Indazole-derivatives as factor Xa inhibitors

ABSTRACT

The present invention relates to a compound of the formula I  
                 
 
     wherein J 1 , J 2 , R 0 , R 1 , R 2 , Q, V, G and M are as defined herein. The compounds of the formula I are valuable pharmacologically active compounds. They exhibit a strong antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can in general be applied in conditions in which an undesired activity of factor Xa and/or factor VIIa is present or for the cure or prevention of which an inhibition of factor Xa and/or factor VIIa is intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

[0001] This application claims the benefit of U.S. ProvisionalApplication No. 60/507,171, filed Sep. 30, 2003.

FIELD OF THE INVENTION

[0002] The present invention relates to a compound of formula I,

[0003] in which J₁, J₂, R¹, R², Q, V, G and M have the meaningsindicated below. The compounds of the formula I are valuablepharmacologically active compounds. They exhibit a strong antithromboticeffect and are suitable, for example, for the therapy and prophylaxis ofcardiovascular disorders like thromboembolic diseases or restenoses.They are reversible inhibitors of the blood clotting enzymes factor Xa(FXa) and/or factor VIIa (FVIIa), and can in general be applied inconditions in which an undesired activity of factor Xa and/or factorVIIa is present or for the cure or prevention of which an inhibition offactor Xa and/or factor VIIa is intended. The invention furthermorerelates to processes for the preparation of compounds of the formula I,their use, in particular as active ingredients in pharmaceuticals, andpharmaceutical preparations comprising them.

BACKGROUND OF THE INVENTION

[0004] Normal haemeostasis is the result of a complex balance betweenthe processes of clot initiation, formation and clot dissolution. Thecomplex interactions between blood cells, specific plasma proteins andthe vascular surface, maintain the fluidity of blood unless injury andblood loss occurs (EP-A-987274). Many significant disease states arerelated to abnormal haemeostasis. For example, local thrombus formationdue to rupture of atheroslerotic plaque is a major cause of acutemyocardial infarction and unstable angina. Treatment of an occlusivecoronary thrombus by either thrombolytic therapy or percutaneousangioplasty may be accompanied by acute thrombolytic reclosure of theaffected vessel.

[0005] There continues to be a need for safe and effective therapeuticanticoagulants to limit or prevent thrombus formation. It is mostdesirable to develop agents that inhibit coagulation without directlyinhibiting thrombin but by inhibiting other steps in the coagulationcascade like factor Xa and/or factor VIIa activity. It is now believedthat inhibitors of factor Xa carry a lower bleeding risk than thrombininhibitors (A. E. P. Adang & J. B. M. Rewinkel, Drugs of the Future2000, 25, 369-383). Low molecular weight, factor Xa-specific bloodclotting inhibitors that are effective but do not cause unwanted sideeffects have been described, for example, in WO-A-95/29189.

[0006] However, besides being an effective factor Xa-specific bloodclotting inhibitor, it is desirable that such inhibitors also havefurther advantageous properties, for instance stability in plasma andliver and selectivity versus other serine proteases whose inhibition isnot intended, such as thrombin. There is an ongoing need for further lowmolecular weight factor Xa specific blood clotting inhibitors, which areeffective and have the above advantages as well.

[0007] Specific inhibition of the factor VIIa/tissue factor catalyticcomplex using monoclonal antibodies (WO-A-92/06711) or a protein such aschloromethyl ketone inactivated factor VIIa (WO-A-96/12800,WO-A-97/47651) is an extremely effective means of controlling thrombusformation caused by acute arterial injury or the thromboticcomplications related to bacterial septicemia There is also experimentalevidence suggesting that inhibition of factor VIIa/tissue factoractivity inhibits restenosis following balloon angioplasty. Bleedingstudies have been conducted in baboons and indicate that inhibition ofthe factor VIIa/tissue factor complex has the widest safety window withrespect to therapeutic effectiveness and bleeding risk of anyanticoagulant approach tested including thrombin, platelet and factor Xainhibition. Certain inhibitors of factor VIIa have already beendescribed. EP-A-987274, for example discloses compounds containing atripeptide unit, which inhibit factor VIIa However, the property profileof these compounds is still not ideal, and there is an ongoing need forfurther low molecular weight factor Via inhibitory blood clottinginhibitors

[0008] The present invention satisfies the above needs by providing anovel compound of formula I, which exhibits better factor Xa and/orfactor VIIA inhibitory activity and are favorable agents with highbioavailability.

SUMMARY OF THE INVENTION

[0009] The present invention relates to a compound of formula I,

[0010] wherein:

[0011] one of J₁ and J₂ is N, and the other is N—Q—R⁰,

[0012] R⁰ is 1) a monocyclic or bicyclic 6- to 14-membered aryl, whereinaryl is mono-, di- or trisubstituted independently of one another by R8,

[0013] 2) a monocyclic or bicyclic 4- to 15-membered heterocyclyl out ofthe group benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl,benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, indazolyl,indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl,phthalazinyl, pteridinyl, purinyl, pyridyl, pyridoimidazolyl,pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl,quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl, wherein saidheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R8, or

[0014] 3) a monocyclic or bicyclic 4- to 15-membered heterocyclyl,containing one, two, three or four heteroatoms chosen from nitrogen,sulfur or oxygen,

[0015] wherein said heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8, and which isadditionally substituted by a monocyclic or bicyclic 4- to 15-memberedheterocyclyl, containing one, two, three or four heteroatoms chosen fromnitrogen, sulfur or oxygen,

[0016] wherein heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8,

[0017] R8 is 1) halogen,

[0018] 2) —NO₂,

[0019] 3) —CN,

[0020] 4) —C(O)—NH₂,

[0021] 5) —OH,

[0022] 6) —NH₂,

[0023] 7) —O—CF₃

[0024] 8) a monocyclic or bicyclic 6- to 14-membered aryl, wherein arylis mono-, di- or trisubstituted independently of one another by halogenor —O—(C₁-C₈)-alkyl,

[0025] 9) —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by halogen, NH₂, —OH or amethoxy residue,

[0026] 10) —O—(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-,di- or trisubstituted independently of one another by halogen, NH₂, —OHor a methoxy residue,

[0027] 11) —SO₂—CH₃ or

[0028] 12) —SO₂—CF₃,

[0029] provided that R8 is at least one halogen, —C(O)—NH₂ or—O—(C₁-C₈)-alkyl residue, if R⁰ is a monocyclic or bicyclic 6- to14-membered aryl,

[0030] the substructure

[0031]  in formula I is

[0032] a 4-to 8 membered saturated, partially unsaturated or aromaticcyclic group containing zero, 1, 2, 3 or 4 heteroatoms chosen fromnitrogen, sulfur or oxygen and is unsubstituted or substituted 1, 2, 3,4, 5 or 6 times by R3 or substituted 1 or 2 times by ═O,

[0033] Q is a direct bond, —(C₀-C₂)-alkylene-C(O)—NR¹⁰—,—NR¹⁰—C(O)—NR¹⁰—, —NR¹⁰—C(O)—, —SO₂—, —(C₁-C₆)-alkylene,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—S—(CH₂)_(n)—, —(CH₂)_(m)—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—CH(OH)—(CH₂)_(n)—,—(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)—,—(C₂-C₃)-alkylene-O—(C₀-C₃)-alkylene-, —(C₂-C₃)-alkylene-S(O)—,—(C₂-C₃)-alkylene-S(O)₂—, —(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—,—(C₂-C₃)-alkylene-S(O)₂—NH—(R¹⁰)—, —(C₂-C₃)-alkylene-N(R¹⁰)— or—(C₀-C₃)-alkylene-C(O)—O—(CH₂)_(m)—,

[0034] wherein R¹⁰ is as defined below, and wherein n and m areindependently of one another identical or different and are the integerszero, 1, 2, 3, 4, 5 or 6, wherein the alkylene residues which are formedby —(CH₂)_(m)— or —(CH₂)_(n)— are unsubstituted or mono-, di- ortrisubstituted independently of one another by halogen, —NH₂, —OH or—(C₃-C₆)-cycloalkylen, wherein cycloalkylen is unsubstituted or mono-,di- or trisubstituted independently of one another by halogen, —NH₂ or—OH;

[0035] R¹ is hydrogen, —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted orsubstituted one to three times by R13; —(C₁-C₃)-alkylene-C(O)—NH—R⁰,—(C₁-C₃)-alkylene-C(O)—O—R¹⁵, amonocyclic or bicyclic 6- to 14-memberedaryl, wherein aryl is mono-, di- or trisubstituted independently of oneanother by R8, wherein R8 is as defined above; a monocyclic or bicyclic4- to 15-membered heterocyclyl, containing one, two, three or fourheteroatoms chosen from nitrogen, sulfur or oxygen;—(C₁-C₃)-perfluoroalkylene, —(C₁-C₃)-alkylene-S(O)—(C₁-C₄)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—(C₁-C₃)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—N(R^(4′))—R^(5′),—(C₁-C₃)-alkylene-O—(C₁-C₄)-alkyl, —(C₀-C₃)-alkylene-(C₃-C₈)-cycloalkyl,or —(C₀-C₃)-alkylene-het, wherein het is a 3- to 7-membered cyclicresidue, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen,sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-,di- or trisubstituted independently of one another by R14,

[0036] R^(4′) and R^(5′) are independent of one another are identical ordifferent and are hydrogen or —(C₁-C₄)-alkyl,

[0037] R² is a direct bond or —(C₁-C₄)-alkylene, or

[0038] R¹ and R³ together with the atoms to which they are bonded canform a 6- to 8-membered cyclic group, containing 1, 2, 3 or 4heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclicgroup is unsubstituted or mono-, di- or trisubstituted independently ofone another by R14, or

[0039] R¹—N—R²—V can form a 4- to 8-membered cyclic group, containing 1,2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, whereinsaid cyclic group is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14,

[0040] R14 is halogen, —OH, ═O, —(C₁-C₈)-alkyl, —(C₁-C₄)-alkoxy, —NO₂,—C(O)—OH, —CN, —NH₂, —C(O)—O—(C₁-C₄)-alkyl,—(C₀-C₈)-alkyl-SO₂—(C₁-C₄)-alkyl,—(C₀-C₈)-alkyl-SO₂—(C₁-C₃)-perfluoroalkyl,—(C₀-C₈)-alkyl-SO₂—N(R¹⁸)—R²¹, —C(O)—NH—(C₁-C₈)-alkyl,—C(O)—N—[(C₁-C₈)-alkyl]₂, —NR¹⁸—C(O)—NH—(C₁-C₈)-alkyl, —C(O)—NH₂,—S—R¹⁸, or —NR¹⁸—C(O)—NH—[(C₁-C₈)-alkyl]₂,

[0041] wherein R¹⁸ and R²¹ are independently from each other hydrogen,—(C₁-C₃)-perfluoroalkyl or —(C₁-C₆)-alkyl,

[0042] V is 1) a 3- to 7-membered cyclic residue, containing 1, 2, 3 or4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein saidcyclic residue is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14,

[0043] 2) a 6- to 14-membered aryl, wherein aryl is unsubstituted ormono-, di- or trisubstituted independently of one another by R14, or

[0044] 3) a monocyclic or bicyclic 4- to 15-membered heterocyclyl,wherein said heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14,

[0045] G is a direct bond, —(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—,—(CH₂)_(m)—CH(OH)—(CH₂)_(n)—, —(CH₂)_(m)—, —(CH₂)_(m)—O—(CH₂)_(n)—,(CH₂)_(m)—C(O)—NR¹⁰(CH₂)_(n)—, —(CH₂)—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—(CH₂)_(n)—, —(CH₂)—S—(CH₂)_(n)—,—(CH₂)_(m)—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—, —(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)— or—(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—,

[0046] n and m are independently of one another identical or differentand are the integers zero, 1,2,3,4, 5 or 6,

[0047] M is 1) hydrogen,

[0048] 2) —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R14,

[0049] 3) —C(O)—N(R11)—R12,

[0050] 4) —(CH₂)_(m)—NR¹⁰,

[0051] 5) a 6- to 14-membered aryl, wherein aryl is unsubstituted ormono-, di- or trisubstituted independently of one another by R14,

[0052] 6) a monocyclic or bicyclic 4- to 15-membered heterocyclyl,wherein heterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14,

[0053] 7) —(C₃-C₈)-cycloalkyl, wherein said cycloalkyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R14, or

[0054] 8) a 3- to 7-membered cyclic residue, containing 1, 2, 3 or 4heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclicresidue is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R14, wherein R14 is defined above,

[0055] R3 is

[0056] 1) hydrogen,

[0057] 2) halogen,

[0058] 3) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0059] 4) —(C₁-C₃)-perfluoroalkyl,

[0060] 5) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0061] 6) —(C₀-C₄)-alkylene-O—R19, wherein R¹⁹ is

[0062] a) hydrogen,

[0063] b) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0064] c) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0065] d) —CF₃, or

[0066] e) —CHF₂,

[0067] 7) —NO₂,

[0068] 8) —CN,

[0069] 9) —SO_(s)—R¹¹, wherein s is 1 or 2,

[0070] 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2,

[0071] 11) —(C₀-C₄)-alkylene-C(O)—R¹¹,

[0072] 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹,

[0073] 13) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹²,

[0074] 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹²,

[0075] 15) —NR¹⁰—SO₂—R¹⁰,

[0076] 16) —S—R¹⁰,

[0077] 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl,

[0078] 18) —C(O)—O—C(R15, R16)—O—C(O)—R17,

[0079] 19)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl,

[0080] 20) —C(O)—O—C(R15, R16)—O—C(O)—O—R17,

[0081] 21) —(C₀-C₄)-alkylene-(C₆-C₁₄)-aryl, wherein aryl is mono-, di-or trisubstituted independently of one another by R13,

[0082] 22) —(C₀-C₄)-alkylene-(C₄-C₁₅)-heterocyclyl, wherein heterocyclylis unsubstituted or mono-, di- or trisubstituted independently of oneanother by R13

[0083] 23) —(C₀-C₄)-alkylene-(C₃-C₈)-cycloalkyl, wherein cycloalkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13,

[0084] 24) —(C₀-C₄)-alkylene-het, wherein het is unsubstituted or mono-,di- or trisubstituted independently of one another by R13,

[0085] 25)—(C₀-C₄)-alkylene-O—CH₂-(C₁-C₃)-perfluoroalkylene-CH₂—O—(C₀-C₄)-alkyl,

[0086] 26) —SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2,

[0087] 27) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³,

[0088] 28) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or

[0089] 29) a residue from the following list

[0090] where Me is methyl, or if two —OR¹⁹ residues are attached toadjacent atoms they can form together with the atoms which they areattached to a 5- or 6-membered ring, which is unsubstituted orsubstituted one, two, three or four times by R13,

[0091] R11and R12 are independently of one another identical ordifferent and are

[0092] 1) hydrogen,

[0093] 2) —(C₁-C₆)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0094] 3) —(C₀-C₆)-alkyl-(C₃-C₈)-cycloalkyl,

[0095] 4) —SO_(t)—R¹⁰, wherein t is 1 or 2,

[0096] 5) —(C₀-C₆)-alkyl-(C₆-C₁₄)-aryl, wherein alkyl and arylindependently from one another are unsubstituted or mono-, di- or trisubstituted by R13,

[0097] 6) —(C₁-C₃)-perfluoroalkyl,

[0098] 7) —O—R¹⁷, or

[0099] 8) —(C₀-C₆)-alkyl-(C₄-C₁₅)-heterocyclyl, wherein alkyl andheterocyclyl independently from one another are unsubstituted or mono-,di- or trisubstituted by R13, or

[0100] R11and R12 together with the nitrogen atom to which they arebonded can form a 4- to 8-membered monocyclic heterocyclic ring which inaddition to the nitrogen atom can contain one or two identical ordifferent ring heteroatoms chosen from oxygen, sulfur and nitrogen;wherein said heterocyclic ring is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0101] R13 is halogen, —NO₂, —CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰,—C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰, —(C₃-C₈)-cycloalkyl,—(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —N(R¹⁰)—S(O), R¹⁰, wherein u is 1or 2, —S—R¹⁰, —SO_(r)—R¹⁰, wherein r is 1 or 2, —S(O)_(v)—N(R¹⁰)—R²⁰,wherein v is 1 or 2, —C(O)—R¹⁰, —(C₁-C₈)-alkyl, —(C₁-C₈)-alkoxy, phenyl,phenyloxy-, —O—CF₃, —(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—R¹⁷,—(C₁-C₄)-alkoxy-phenyl, —(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—O—R¹⁷,—(C₁-C₃)-perfluoroalkyl, —O—R15, —NH—C(O)—NH—R¹⁰, —NH—C(O)—O—R¹⁰, or aresidue from the following list

[0102] R¹⁰ and R²⁰ are independently of one another hydrogen,—(C₁-C₆)-alkyl, —(C₀-C₄)-alkyl-OH, —(C₀-C₄)-alkyl-O—(C₁-C₄)-alkyl or—(C₁-C₃)-perfluoroalkyl,

[0103] R15 and R16 are independently of one another hydrogen,—(C₁-C₆)-alkyl, or together with the carbon atom to which they arebonded they can form a 3- to 6 membered carbocyclic ring which isunsubstituted or substituted one to three times by R¹⁰, and

[0104] R17 is —(C₁-C₆)-alkyl, —(C₁-C₆)-alkyl-OH,—(C₁-C₆)-alkyl-O—(C₁-C₆)-alkyl, —(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-O—(C₁-C₈)-alkyl-(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-(C₃-C₈)-cycloalkyl, wherein said cycloalkyl ring isunsubstituted or substituted one, two or three times by —OH,—O—(C₁-C₄)-alkyl or R¹⁰,

[0105] in all its stereoisomeric forms and mixtures thereof in anyratio, and its physiologically tolerable salts.

DETAILED DESCRIPTION OF THE INVENTION

[0106] Definition of Terms

[0107] As used above, and throughout the description of the invention,the following terms, unless otherwise indicated, shall be understood tohave the following meanings.

[0108] In general, the meaning of any group, residue, heteroatom, numberetc., which can occur more than once in the compounds of the formula I,is independent of the meaning of this group, residue, heteroatom, numberetc. in any other occurrence. All groups, residues, heteroatoms, numbersetc., which can occur more than once in the compounds of the formula Ican be identical or different. As used herein, the term alkyl is to beunderstood in the broadest sense to mean hydrocarbon residues which canbe linear, i.e. straight-chain, or branched and which can be acyclic orcyclic residues or comprise any combination of acyclic and cyclicsubunits. Further, the term alkyl as used herein expressly includessaturated groups as well as unsaturated groups which latter groupscontain one or more, for example one, two or three, double bonds and/ortriple bonds, provided that the double bonds are not located within acyclic alkyl group in such a manner that an aromatic system results. Allthese statements also apply if an alkyl group occurs as a substituent onanother residue, for example in an alkyloxy residue, an alkyloxycarbonylresidue or an arylalkyl residue. Examples of “—(C₁-C₈)-alkyl” or“—(C₁-C₈)-alkylene” are alkyl residues containing 1, 2, 3, 4, 5, 6, 7 or8 carbon atoms are methyl, methylene, ethyl, ethylene, propyl,propylene, butyl, butylene, pentyl, pentylene, hexyl, heptyl or octyl,the n-isomers of all these residues, isopropyl, isobutyl, 1-methylbutyl,isopentyl, neopentyl, 2,2-dimethylbutyl, 2-methylpentyl, 3-methylpentyl,isohexyl, sec-butyl, tBu, tert-pentyl, sec-butyl, tert-butyl ortert-pentyl. The term “—(C₀-C₆)-alkyl” or “—(C₀-C₈)-alkylene” is ahydrocarbon residues containing 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms.The term “—C₀-alkyl ” or “—C₀-alkylene” is a covalent bond.

[0109] Unsaturated alkyl residues are, for example, alkenyl residuessuch as vinyl, 1-propenyl, 2-propenyl (=allyl), 2-butenyl, 3-butenyl,2-methyl-2-butenyl, 3-methyl-2-butenyl, 5-hexenyl or 1,3-pentadienyl, oralkynyl residues such as ethynyl, 1-propynyl, 2-propynyl (=propargyl) or2-butynyl. Alkyl residues can also be unsaturated when they aresubstituted.

[0110] Examples of —(C₃-C₈)-cycloalkyl cyclic alkyl residues arecycloalkyl residues containing 3, 4, 5, 6, 7 or 8 ring carbon atoms likecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyloheptyl orcyclooctyl, which can also be substituted and/or unsaturated.Unsaturated cyclic alkyl groups and unsaturated cycloalkyl groups like,for example, cyclopentenyl or cyclohexenyl can be bonded via any carbonatom.

[0111] The terms “a monocyclic or bicyclic 6- to 14-membered aryl” or“—(C₆-C₁₄)-aryl” are understood as meaning aromatic hydrocarbon radicalscontaining from 6 to 14 carbon atoms in the ring. Examples of—(C₆-C₁₄)-aryl radicals are phenyl, naphthyl, for example 1-naphthyl and2-naphthyl, biphenylyl, for example 2-biphenylyl, 3-biphenylyl and4-biphenylyl, anthryl or fluorenyl. Biphenylyl radicals, naphthylradicals and, in particular, phenyl radicals are preferred arylradicals.

[0112] The terms “mono- or bicyclic 4- to 15-membered heterocyclyl” or“—(C₄-C₁₅)-heterocyclyl” refer to heterocycles in which one or more ofthe 4 to 15 ring carbon atoms are replaced by heteroatoms such asnitrogen, oxygen or sulfur.

[0113] Examples are acridinyl, azaindole (1H-pyrrolopyridinyl),8-aza-bicyclo[3.2.1]oct-3-yl, azabenzimidazolyl, azaspirodecanyl,azepinyl, azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl,benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl,benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl,carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl,cinnolinyl, decahydrochinolinyl, 4,5-dihydrooxazolinyl, dioxazolyl,dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl,imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl,isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl),isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl,isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl,morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl,1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl,oxazolyl, oxetanyl, oxocanyl, phenanthridinyl, phenanthrolinyl,phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl,piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazinyl,pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazolyl,pyridoimidazolyl, pyridothiazolyl, pyridinyl, pyridyl, pyrimidinyl,pyrrolidinyl, pyrrolidinonyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl,quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl,tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl,tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, 1λ6-thiomorpholinyl, thiophenolyl,thiophenyl, thiopyranyl, 1,2,3-triazinyl, 1,2,4-triazinyl,1,3,5-triazinyl, 1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl,1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl.

[0114] Preferred are heterocyclyls, such as benzimidazolyl,1,3-benzodioxolyl, benzofuranyl, benzothiazolyl, benzothiophenyl,benzoxazolyl, chromanyl, cinnolinyl, 2-fuiryl, 3-furyl; imidazolyl,indolyl, indazolyl, isochromanyl, isoindolyl, isoquinolinyl,isothiazolyl, isoxazolyl, oxazolyl, phthalazinyl, pteridinyl, purinyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, pyridopyridinyl,pyridopyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidinyl,pyrrolyl; 2-pyrrolyl, 3-pyrrolyl, quinolinyl, quinazolinyl,quinoxalinyl, tetrazolyl, thiazolyl, 2-thienyl and 3-thienyl.

[0115] Also preferred are:

[0116] The terms “het” or “a 3- to 7-membered cyclic residue, containingup to 1, 2, 3 or 4 heteroatoms” refer to structures of heterocycleswhich can be derived from compounds such as azepine, azetidine,aziridine, azirine, 1,4 diazepane, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole,1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline,imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole,isoxazoline, isoxazolidine, 2-isoxazoline, ketomorpholine,ketopiperazine, morpholine, 1,2-oxa-thiepane, 1,2-oxathiolane,1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole,oxaziridine, oxetan, oxirane, piperazine, piperidine, pyran, pyrazine,pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine,pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydrofuran,tetrahydropyran, tetrahydropyridine, tetrazine, tetrazole, thiadiazinethiadiazole, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole,thiazole, thiazolidine, thiazoline, thienyl, thietan, thiomorpholine,thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole or 1,2,4-triazole.

[0117] The term “R¹—N—R²—V can form a 4- to 8-membered cyclic group ” or“R¹I¹ and R¹² together with the nitrogen atom to which they are bondedcan form a 4- to 8-membered monocyclic heterocyclic ring which inaddition to the nitrogen atom can contain one or two identical ordifferent ring heteroatoms chosen from oxygen, sulfur and nitrogen”refer to structures of heterocycles which can be derived from compoundssuch as azepane, azepine, azetidine, dioxazole, dioxazine,1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole,imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline,isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine,morpholine, [1,4]oxazepane, oxazole, piperazine, piperidine, pyrazine,pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine,pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine,tetrazine, tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline,thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole or 1,2,4-triazole.

[0118] The term “R¹⁵ and R¹⁶ together with the carbon atom to which theyare bonded can form a 3- to 6 membered carbocyclic ring” refer tostructures, which can be derived from compounds such as cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl.

[0119] The term “substructure

[0120] in formula I or the “substructure D” are a 4-to 8 memberedsaturated, partially unsaturated or aromatic cyclic group containingzero, 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen”refer to structures, which can be derived from compounds such asazepane, azetidine, azetine, azocane, azocane-2-one, cyclobutyl,cyclooctane, cyclooctene, cyclopentyl, cyclohexyl, cycloheptyl,cyclooctyl, 1,2-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine,[1,4]diazocane, [1,2]diazocan-3-one, [1,3]diazocan-2-one, dioxazole,dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan, imidazole,imidazoline, imidazolidine, isothiazole, isothiazolidine, isothiazoline,isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine,morpholine, 1,4-oxaazepane, 1,2-oxa-thiepane, 1,2-oxathiolan,1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, [1,4]oxazocane,[1,3]oxazocan-2-one, oxetan, oxocane, oxocan-2-one, piperazine,piperidine, phenyl, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, 5,6,7,8-tetrahydro-1H-azocin-2-one, tetrahydrofuran,tetrahydropyran, tetrahydropyridine, tetrazine, thiadiazine thiadiazole,1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole,thiazolidine, thiazoline, thietan, thiocane, thiocane-1,1-dioxide,thiocane-1-oxide, thiocan-2-one, thiomorpholine, thiopyran,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or1,2,4-triazole.

[0121] The term “substructure D” is a 5 to 6 membered saturated,partially unsaturated or aromatic cyclic group containing zero, 1, 2, 3or 4 heteroatoms chosen from nitrogen, sulfur or oxygen” refer tostructures, which can be derived from compounds such as cyclopentyl,cyclohexyl, dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane,furan, imidazole, imidazoline, imidazolidine, isothiazole,isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine,2-isoxazoline, ketopiperazine, morpholine, ketomorpholine,1,2-oxathiolan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole,piperazine, piperidine, phenyl, pyran, pyrazine, pyrazole, pyrazoline,pyrazolidine, pyrazine, pyrazinone, pyridazine, pyridazone, pyridine,pyridone, pyrimidine, pyrimidone, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, tetrahydrofuran, tetrahydropyran, tetrahydropyridine,tetrazine, tetrazole, thiadiazine thiadiazole, 1,2-thiazine,1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine,thiazoline, thiomorpholine, thiopyran, tetrazine, tetrazole,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or1,2,4-triazole.

[0122] The term “R¹ and R³ together with the atoms to which they arebonded can form a 6- to 8-membered cyclic group, containing up to 1, 2,3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen” refers tostructures of heterocycles which can be derived from compounds such asazocane, azocane-2-one, cyloheptyl cyclohexyl, cyclooctane, cyclooctene,1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine,[1,4]diazocane, [1,2]diazocan-3-one, [1,3]diazocan-2-one, dioxazine,[1,4]dioxocane, dioxole, ketopiperazine, morpholine, 1,2-oxa-thiepane,1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, [1,4]oxazocane,[1,3]oxazocan-2-one, oxocane, oxocan-2-one, phenyl, piperazine,piperidine, pyran, pyrazine, pyridazine, pyrimidine,5,6,7,8-tetrahydro-1H-azocin-2-one or thiomorpholine.

[0123] The fact that many of the before-listed names of heterocycles arethe chemical names of unsaturated or aromatic ring systems does notimply that the, the 4-15 membered mono- or polycyclic group could onlybe derived from the respective unsaturated ring system. The names hereonly serve to describe the ring system with respect to ring size and thenumber of the heteroatoms and their relative positions. As explainedabove, the 4-15 membered mono- or polycyclic group can be saturated orpartially unsaturated or aromatic, and can thus be derived not only fromthe before-listed heterocycles themselves but also from all theirpartially or completely hydrogenated analogues and also from their morehighly unsaturated analogues if applicable. As examples of completely orpartially hydrogenated analogues of the before-listed heterocycles fromwhich this group may be derived the following may be mentioned:pyrroline, pyrrolidine, tetrahydrofuran, tetrahydrothiophene,dihydropyridine, tetrahydropyridine, piperidine, 1,3-dioxolane,2-imidazoline, imidazolidine, 4,5-dihydro-1,3-oxazol, 1,3-oxazolidine,4,5-dihydro-1,3-thiazole, 1,3-thiazolidine, perhydro-1,4-dioxane,piperazine, perhydro-1,4-oxazine (=morpholine), perhydro-1,4-thiazine(=thiomorpholine), perhydroazepine, indoline, isoindoline,1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, etc.

[0124] The term “—(C₁-C₃)-perfluoroalkyl” is a partial or totallyfluorinated alkyl-residue, which can be derived from residues such as—CF₃, —CHF₂, —CH₂F, —CHF—CF₃, —CHF—CHF₂, —CHF—CH₂F, —CH₂—CF₃, —CH₂—CHF₂,—CH₂—CH₂F, —CF₂—CF₃, —CF₂—CHF₂, —CF₂—CH₂F, —CH₂—CHF—CF₃, —CH₂—CHF—CHF₂,—CH₂—CHF—CH₂F, —CH₂—CH₂—CF₃, —CH₂—CH₂—CHF₂, —CH₂—CH₂—CH₂F, —CH₂—CF₂—CF₃,—CH₂—CF₂—CHF₂, —CH₂—CF₂—CH₂F, —CHF—CHF—CF₃, —CHF—CHF—CHF₂,—CHF—CHF—CH₂F, —CHF—CH₂—CF₃, —CHF—CH₂—CHF₂, —CHF—CH₂—CH₂F, —CHF—CF₂—CF₃,—CHF—CF₂—CHF₂, —CHF—CF₂—CH₂F, —CF₂—CHF—CF₃, —CF₂—CHF—CHF₂,—CF₂—CHF—CH₂F, —CF₂—CH₂—CF₃, —CF₂—CH₂—CHF₂, —CF₂—CH₂—CH₂F, —CF₂—CF₂—CF₃,—CF₂—CF₂—CHF₂ or —CF₂—CF₂—CH₂F.

[0125] The term “—(C₁-C₃)-perfluoroalkylene” is a partial or totallyfluorinated alkylene-residue, which can be derived from residues such as—CF₂—, —CHF—, —CHF—CHF₂—, —CHF—CHF—, —CH₂—CF₂—, —CH₂—CHF—, —CF₂—CF₂—,—CF₂—CHF—, —CH₂—CHF—CF₂—, —CH₂—CHF—CHF—, —CH₂—CH₂—CF₂—, —CH₂—CH₂—CHF,—CH₂—CF₂—CF₂—, —CH₂—CF₂—CHF—, —CHF—CHF—CF₂—, —CHF—CHF—CHF—,—CHF—CH₂—CF₂—, —CHF—CH₂—CHF—, —CHF—CF₂—CF₂—, —CHF—CF₂—CHF—,—CF₂—CHF—CF₂—, —CF₂—CHF—CHF—, —CF₂—CH₂—CF₂—, —CF₂—CH₂—CHF—,—CF₂—CF₂—CF₂—, or —CF₂—CF₂—CHF.

[0126] Halogen is fluorine, chlorine, bromine or iodine, preferablyfluorine, chlorine or bromine, particularly preferably chlorine orbromine.

[0127] The term “oxo-residue” or “═O” refers to residues such ascarbonyl (—C(O)—) or nitroso (—N═O).

[0128] Optically active carbon atoms present in the compounds of theformula I can independently of each other have R configuration or Sconfiguration. The compounds of the formula I can be present in the formof pure enantiomers or pure diastereomers or in the form of mixtures ofenantiomers and/or diastereomers, for example in the form of racemates.The present invention relates to pure enantiomers and mixtures ofenantiomers as well as to pure diastereomers and mixtures ofdiastereomers. The invention comprises mixtures of two or of more thantwo stereoisomers of the formula I, and it comprises all ratios of thestereoisomers in the mixtures. In case the compounds of the formula Ican be present as E isomers or Z isomers (or cis isomers or transisomers) the invention relates both to pure E isomers and pure Z isomersand to E/Z mixtures in all ratios. The invention also comprises alltautomeric forms of the compounds of the formula I.

[0129] Diastereomers, including E/Z isomers, can be separated into theindividual isomers, for example, by chromatography. Racemates can beseparated into the two enantiomers by customary methods, for example bychromatography on chiral phases or by resolution, for example bycrystallization of diastereomeric salts obtained with optically activeacids or bases. Stereochemically uniform compounds of the formula I canalso be obtained by employing stereochemically uniform startingmaterials or by using stereoselective reactions.

[0130] Physiologically tolerable salts of the compounds of formula I arenontoxic salts that are physiologically acceptable, in particularpharmaceutically utilizable salts. Such salts of compounds of theformula I containing acidic groups, for example a carboxyl group COOH,are for example alkali metal salts or alkaline earth metal salts such assodium salts, potassium salts, magnesium salts and calcium salts, andalso salts with physiologically tolerable quaternary ammonium ions suchas tetramethylammonium or tetraethylammonium, and acid addition saltswith ammonia and physiologically tolerable organic amines, such asmethylamine, dimethylamine, trimethylamine, ethylamine, triethylamine,ethanolamine or tris-(2-hydroxy-ethyl)amine. Basic groups contained inthe compounds of the formula I, for example amino groups or guanidinogroups, form acid addition salts, for example with inorganic acids suchas hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid orphosphoric acid, or with organic carboxylic acids and sulfonic acidssuch as formic acid, acetic acid, oxalic acid, citric acid, lactic acid,malic acid, succinic acid, malonic acid, benzoic acid, maleic acid,fumaric acid, tartaric acid, methanesulfonic acid or p-toluenesulfonicacid. Compounds of the formula I, which simultaneously contain a basicgroup and an acidic group, for example a guanidino group and a carboxylgroup, can also be present as zwitterions (betaines), which are likewiseincluded in the present invention.

[0131] Patient includes both human and other mammals.

[0132] Pharmaceutically effective amount means an amount of the compoundaccording to the invention effective in producing the desiredtherapeutic effect.

[0133] Particular or Preferred Embodiments

[0134] One particular embodiment of the present invention also relatesto a compound of formula I, wherein

[0135] one of J₁ and J₂ is N, and the other is N—Q—R⁰,

[0136] R⁰ is 1) a monocyclic or bicyclic 6- to 14-membered aryl, whereinaryl is mono-, di- or trisubstituted independently of one another by R8,

[0137] 2) a monocyclic or bicyclic 4- to 15-membered heterocyclyl out ofthe group benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl,benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl, indazolyl,indolyl, isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl,phthalazinyl, pteridinyl, purinyl, pyridyl, pyridoimidazolyl,pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl,quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl, wherein saidheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R8, or

[0138] 3) a monocyclic or bicyclic 4- to 15-membered heterocyclyl,containing one, two, three or four heteroatoms chosen from nitrogen,sulfur or oxygen,

[0139] wherein said heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8, and which isadditionally substituted by a monocyclic or bicyclic 4- to 15-memberedheterocyclyl, containing one, two, three or four heteroatoms chosen fromnitrogen, sulfur or oxygen,

[0140] wherein heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8,

[0141] R8 is 1) halogen,

[0142] 2) —NO₂,

[0143] 3) —CN,

[0144] 4) —C(O)—NH₂,

[0145] 5) —OH,

[0146] 6) —NH₂,

[0147] 7) —O—CF₃

[0148] 8) a monocyclic or bicyclic 6- to 14-membered aryl, wherein arylis mono-, di- or trisubstituted independently of one another by halogenor —O—(C₁-C₈)-alkyl,

[0149] 9) —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by halogen, NH₂, —OH or amethoxy residue, or

[0150] 10) —O—(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-,di- or trisubstituted independently of one another by halogen, NH₂, —OHor a methoxy residue,

[0151] 11) —SO₂—CH₃ or

[0152] 12) —SO₂—CF₃, provided that R8 is at least one halogen, —C(O)—NH₂or —O—(C₁-C₈)-alkyl residue, if R⁰ is a

[0153] monocyclic or bicyclic 6- to 14-membered aryl, substructure D isa 5- to 6 membered saturated, partially unsaturated or aromatic cyclicgroup containing zero, 1, 2, 3 or 4 heteroatoms chosen from nitrogen,sulfur or oxygen and is substituted 1, 2, 3, 4, 5 or 6 times by R3,

[0154] Q is a direct bond, —(C₀-C₂)-alkylene-C(O)—NR¹⁰—,—NR¹⁰—C(O)—NR¹⁰—, —NR¹⁰—C(O)—, —SO₂—, —(C₁-C₆)-alkylene,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—S—(CH₂)_(n)—, —(CH₂)_(m)—C(O)—(CH₂)_(n)—, —(CH₂)_(m)—SO₂—NR—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—CH(OH)—(CH₂)_(n)—,—(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)—,—(C₂-C₃)-alkylene-O—(C₀-C₃)-alkylene-, —(C₂-C₃)-alkylene-S(O)—,—(C₂-C₃)-alkylene-S(O)₂—, —(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—,—(C₂-C₃)-alkylene-S(O)₂—NH—(R¹⁰)—, —(C₂-C₃)-alkylene-N(R¹⁰)— or—(C₀-C₃)-alkylene-C(O)—O—(CH₂)_(m)—,

[0155] wherein R¹⁰ is as defined below, and wherein n and m areindependently of one another identical or different and are the integerszero, 1, 2, 3, 4, 5 or 6, wherein the alkylene residues which are formedby —(CH₂)_(m)— or —(CH₂)_(n)— are unsubstituted or mono-, di- ortrisubstituted independently of one another by halogen, —NH₂ or —OH; or—(C₃-C₆)-cycloalkylen, wherein cycloalkylen is unsubstituted or mono-,di- or trisubstituted independently of one another by halogen, —NH₂ or—OH;

[0156] R¹ is hydrogen, —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted orsubstituted one to three times by R13; —(C₁-C₃)-alkylene-C(O)—NH—R⁰,—(C₁-C₃)-alkylene-C(O)—O—R15, a monocyclic or bicyclic 6- to 14-memberedaryl, wherein aryl is mono-, di- or trisubstituted independently of oneanother by R8, wherein R8 is as defined above; a monocyclic or bicyclic4- to 15-membered heterocyclyl, containing one, two, three or fourheteroatoms chosen from nitrogen, sulfur or oxygen;—(C₁-C₃)-perfluoroaikylene,

[0157] —(C₁-C₃)-alkylene-S(O)—(C₁-C₄)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—(C₁-C₃)-alkyl,

[0158] —(C₁-C₃)-alkylene-S(O)₂—N(R^(4′))—R^(5′),—(C₁-C₃)-alkylene-O—(C₁-C₄)-alkyl,

[0159] —(C₀-C₃)-alkylene-(C₃-C₈)-cycloalkyl, or —(C₀-C₃)-alkylene-het,wherein het is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14,

[0160] R^(4′) and R^(5′) are independent of one another are identical ordifferent and are hydrogen or —(C₁-C₄)-alkyl,

[0161] R² is a direct bond or —(C₁-C₄)-alkylene, or

[0162] R¹ and R3 together with the atoms to which they are bonded canform a 6- to 8-membered cyclic group, containing up to 1, 2, 3 or 4heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclicgroup is unsubstituted or mono-, di- or trisubstituted independently ofone another by R14, or

[0163] R¹—N—R²—V can form a 4- to 8-membered cyclic group, containing 1,2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, whereinsaid cyclic group is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14,

[0164] R14 is halogen, —OH, ═O, —(C₁-C₈)-alkyl, —(C₁-C₄)-alkoxy, —NO₂,—C(O)—OH, —CN, —NH₂,

[0165] —C(O)—O—(C₁-C₄)-alkyl, —(C₀-C₈)-alkyl-SO₂—(C₁-C₄)-alkyl,

[0166] —(C₀-C₈)-alkyl-SO₂—(C₁-C₃)-perfluoroalkyl,—(C₀-C₈)-alkyl-SO₂—N(R¹⁸)—R²¹,

[0167] —C(O)—NH—(C₁-C₈)-alkyl, —C(O)—N—[(C₁-C₈)-alkyl]₂,—NR¹⁸—C(O)—NH—(C₁-C₈)-alkyl,

[0168] —C(O)—NH₂, —S—R¹⁸, or —NR¹⁸—C(O)—NH—[(C₁-C₈)-alkyl]₂,

[0169] wherein R¹⁸ and R²¹ are independently from each other hydrogen,—(C₁-C₃)-perfluoroalkyl or QC₁-C₆)-alkyl,

[0170] V is 1) a 3- to 7-membered cyclic residue, containing 1, 2, 3 or4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein saidcyclic residue is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14,

[0171] 2) a 6- to 14-membered aryl, wherein aryl is unsubstituted ormono-, di- or trisubstituted independently of one another by R14, or

[0172] 3) a monocyclic or bicyclic 4- to 15-membered heterocyclyl,wherein said heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14,

[0173] G is a direct bond, —(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—,—(CH₂)_(m)—CH(OH)—(CH₂)_(n)—, —(CH₂)_(m)—, —(CH₂)_(m)—O—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—NR¹⁰ (CH₂)_(n)—, —(CH₂)—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—(CH₂)_(n)—, —(CH₂)—S—(CH₂)_(n)—,—(CH₂)_(m)—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—, —(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)— or—(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—,

[0174] n and m are independently of one another identical or differentand are the integers zero, 1, 2, 3, 4, 5 or 6,

[0175] M is 1) hydrogen,

[0176] 2) —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R14,

[0177] 3) —C(O)—N(R¹¹)—R¹²,

[0178] 4) —(CH₂)_(m)—NR¹⁰,

[0179] 5) —(C₆-C₁₄)-aryl, wherein aryl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14,

[0180] 6) —(C₄-C₁₅)-heterocyclyl, wherein heterocyclyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R14,

[0181] 7) —(C₃-C₈)-cycloalkyl, wherein said cycloalkyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R14, or

[0182] 8) a 3- to 7-membered cyclic residue, containing up to 1, 2, 3 or4 heteroatoms chosen from nitrogen, sulfur or oxygen, wherein saidcyclic residue is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14, wherein R¹⁴ is defined above,

[0183] R3 is

[0184] 1) hydrogen,

[0185] 2) halogen,

[0186] 3) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0187] 4) —(C₁-C₃)-perfluoroalkyl,

[0188] 5) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0189] 6) —(C₀-C₄)-alkylene-O—R¹⁹, wherein R¹⁹ is

[0190] a) hydrogen,

[0191] b) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0192] c) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0193] d) —CF₃,

[0194] e) —CHF₂,

[0195] 7) —NO₂,

[0196] 8) —CN,

[0197] 9) —SO_(s)—R¹¹, wherein s is 1 or 2,

[0198] 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2,

[0199] 11) —(C₀-C₄)-alkylene-C(O)—R¹¹,

[0200] 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹,

[0201] 13) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹²,

[0202] 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹²,

[0203] 15) —NR¹⁰—SO₂—R¹⁰,

[0204] 16) —S—R¹⁰,

[0205] 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl,

[0206] 18) —C(O)—O—C(R15, R16)—O—C(O)—R17,

[0207] 19)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl,

[0208] 20) —C(O)—O—C(R15, R16)—O—C(O)—O—R^(17,)

[0209] 21) —(C₀-C₄)-alkylene-(C₆-C₁₄)-aryl, wherein aryl is mono-, di-or trisubstituted independently of one another by R13,

[0210] 22) —(C₀-C₄)-alkylene-(C₄-C₁₅)-heterocyclyl, wherein heterocyclylis unsubstituted or mono-, di- or trisubstituted independently of oneanother by R13

[0211] 23) —(C₀-C₄)-alkylene-(C₃-C₈)-cycloalkyl, wherein cycloalkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13,

[0212] 24) —(C₀-C₄)-alkylene-het, wherein het is unsubstituted or mono-,di- or trisubstituted independently of one another by R13,

[0213] 25)—(C₀-C₃)-alkylene-O—CH₂-(C₁-C₃)-perfluoroalkylene-CH₂—O—(C₀-C₃)-alkyl,

[0214] 26) —SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2,

[0215] 27) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³,

[0216] 28) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or

[0217] 29) a residue from the following list

[0218] wherein Me is methyl, or if two —OR¹⁹ residues are attached toadjacent atoms they can form together with the atoms which they areattached to a 5- or 6-membered ring, which is unsubstituted orsubstituted one, two, three or four times by R13,

[0219] R11 and R12 are independently of one another identical ordifferent and are

[0220] 1) hydrogen,

[0221] 2) —(C₁-C₆)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0222] 3) —(C₀-C₆)-alkyl-(C₃-C₈)-cycloalkyl,

[0223] 4) —SO_(t)—R¹⁰, wherein t is 1 or 2,

[0224] 5) —(C₀-C₆)-alkyl-(C₆-C₁₄)-aryl, wherein alkyl and arylindependently from one another are unsubstituted or mono-, di- ortrisubstituted by R13,

[0225] 6) —(C₁-C₃)-perfluoroalkyl,

[0226] 7) —O—R¹⁷, or

[0227] 8) —(C₀-C₆)-alkyl-(C₄-C₁₅)-heterocyclyl, wherein alkyl andheterocyclyl independently from one another are unsubstituted or mono-,di- or trisubstituted by R13, or

[0228] R11 and R12 together with the nitrogen atom to which they arebonded can form a 4- to 8-membered monocyclic heterocyclic ring which inaddition to the nitrogen atom can contain one or two identical ordifferent ring heteroatoms chosen from oxygen, sulfur and nitrogen;wherein said heterocyclic ring is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0229] R13 is halogen, —NO₂, —CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰,—C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰, —(C₃-C₈)-cycloalkyl,—(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —N(R¹⁰)—(O)_(u)—R¹⁰, wherein u is 1or 2, —S—R¹⁰, —SO_(r)—R¹⁰, wherein r is 1 or 2, —S(O)_(v)—N(R¹⁰)—R²⁰,wherein v is 1 or 2, —C(O)—R¹⁰, —(C₁-C₈)-alkyl, —(C₁-C₈)-alkoxy, phenyl,phenyloxy-, —O—CF₃, —(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—R17,—(C₁-C₄)-alkoxy-phenyl, —(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—O—R¹⁷,—(C₁-C₃)-perfluoroalkyl, —O—R15, —NH—C(O)—NH—R¹⁰, —NH—C(O)—O—R¹⁰, or aresidue from the following list

[0230] R¹⁰ and R²⁰ are independently of one another hydrogen,—(C₁-C₆)-alkyl or —(C₁-C₃)-perfluoroalkyl,

[0231] R15 and R16 are independently of one another hydrogen,—(C₁-C₆)-alkyl, or together with the carbon atom to which they arebonded they can form a 3- to 6 membered carbocyclic ring which isunsubstituted or substituted one to three times by R¹⁰, and

[0232] R17 is —(C₁-C₆)-alkyl, —(C₁-C₆)-alkyl-OH,—(C₁-C₆)-alkyl-O—(C₁-C₆)-alkyl, —(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-O—(C₁-C₈)-alkyl-(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-(C₃-C₈)-cycloalkyl, wherein said cycloalkyl ring isunsubstituted or substituted one, two or three times by —OH,—O—(C₁-C₄)-alkyl or R¹⁰,

[0233] in all its stereoisomeric forms and mixtures thereof in anyratio, and its physiologically tolerable salts

[0234] Another particular embodiment of the present invention relates toa compound of formula I, wherein

[0235] one of J₁ and J₂ is N, and the other is N—Q—R⁰,

[0236] R⁰ is 1) a monocyclic or bicyclic 6- to 14-membered aryl out ofthe group phenyl, naphthyl, biphenylyl, anthryl or fluorenyl, whereinaryl is mono-, di- or trisubstituted independently of one another by R8,

[0237] 2) a heterocyclyl out of the group benzimidazolyl,1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl,benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl,isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl,pteridinyl, purinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl,pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or1,4,5,6-tetrahydro-pyridazinyl, wherein said heterocyclyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R8, or

[0238] 3) a heterocyclyl, wherein heterocyclyl is selected out of thegroup acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl,azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl,4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl,decahydrochinolinyl, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl,1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl,imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl,isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl,isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl,naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,2-oxazinyl,1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl,phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl,tetrahydroisoquinolinyl, tetrahydroquinolinyl,1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl,1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl,

[0239] wherein said heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8, and

[0240] which is additionally substituted by a heterocyclyl selected outof the group acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl,azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl,4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl,decahydrochinolinyl, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl,1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl,imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl,isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl,isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl,naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,2-oxazinyl,1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl,phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl,tetrahydroisoquinolinyl, tetrahydroquinolinyl,1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl,1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl,

[0241] wherein heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8,

[0242] R8 is 1) halogen,

[0243] 2) —NO₂,

[0244] 3) —CN,

[0245] 4) —C(O)—NH₂,

[0246] 5) —OH,

[0247] 6) —NH₂,

[0248] 7) —O—CF₃

[0249] 8) a monocyclic or bicyclic 6- to 14-membered aryl, wherein arylis as defined above and wherein aryl is mono-, di- or trisubstitutedindependently of one another by halogen or —O—(C₁-C₈)-alkyl,

[0250] 9) —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by halogen, NH₂, —OH or amethoxy residue, or

[0251] 10) —O—(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-,di- or trisubstituted independently of one another by halogen, NH₂, —OHor a methoxy residue,

[0252] 11) —SO₂—CH₃ or

[0253] 12) —SO₂—CF₃,

[0254] provided that R8 is at least one halogen, —C(O)—NH₂ or—O—(C₁-C₈)-alky1 residue, if R⁰ is a monocyclic or bicyclic 6- to14-membered aryl, wherein aryl is as defined above,

[0255] substructure D is a residue selected out of the group azetidine,azetine, azocane, azocane-2-one, cyclobutyl, cyclooctane, cyclooctene,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 1,4-diazepane,1,2-diazepine, 1,3-diazepine, 1,4-diazepine, [1,4]diazocane,[1,2]diazocan-3-one, [1,3]diazocan-2-one, dioxazole, dioxazine, dioxole,1,3-dioxolene, 1,3-dioxolane, furan, imidazole, imidazoline,imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole,isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine,1,2-oxa-thiepane, 1,2-oxathiolan, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine,oxazole, [1,4]oxazocane, [1,3]oxazocan-2-one, oxetan, oxocane,oxocan-2-one, piperazine, piperidine, phenyl, pyran, pyrazine, pyrazole,pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole,pyrrolidine, pyrrolidinone, pyrroline,5,6,7,8-tetrahydro-1H-azocin-2-one, tetrahydrofuran, tetrahydropyran,tetrahydropyridine, tetrazine, thiadiazine, thiadiazole, 1,2-thiazine,1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine,thiazoline, thietan, thiocane, thiocane-1,1-dioxide, thiocane-1-oxide,thiocan-2-one, thiomorpholine, thiophene, thiopyran, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole and isunsubstituted or substituted 1, 2, 3, 4, 5 or 6 times by R3,

[0256] Q is a direct bond, —(C₀-C₂)-alkylene-C(O)—NR¹⁰—,—NR¹⁰—C(O)—NR¹⁰—, —NR¹⁰—C(O)—, —SO₂—, —(C₁-C₆)-alkylene,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—S—(CH₂)_(n)—, —(CH₂)_(m)—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—CH(OH)—(CH₂)_(n)—,—(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)—,—(C₂-C₃)-alkylene-O—(C₀-C₃)-alkylene-, —(C₂-C₃)-alkylene-S(O)—,—(C₂-C₃)-alkylene-S(O)₂—, —(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—,—(C₂-C₃)-alkylene-S(O)₂—NH—(R¹⁰)—, —(C₂-C₃)-alkylene-N(R¹⁰)— or—(C₀-C₃)-alkylene-C(O)—O—(CH₂)_(m)—,

[0257] wherein R¹⁰ is as defined below, and wherein n and m areindependently of one another identical or different and are the integerszero, 1, 2, 3, 4, 5 or 6, wherein the alkylene residues which are formedby —(CH₂)_(m)— or —(CH₂)_(n)— are unsubstituted or mono-, di- ortrisubstituted independently of one another by halogen, —NH₂ or —OH; or—(C₃-C₆)-cycloalkylen, wherein cycloalkylen is unsubstituted or mono-,di- or trisubstituted independently of one another by-halogen, —NH₂ or—OH;

[0258] R¹ is hydrogen, —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted orsubstituted one to three times by R13; —(C₁-C₃)-alkylene-C(O)—NH—R⁰,—(C₁-C₃)-alkylene-C(O)—O—R15, an aryl out of the group phenyl, naphthyl,biphenylyl, anthryl or fluorenyl, wherein aryl is mono-, di- ortrisubstituted independently of one another by R8, wherein R8 is asdefined above;

[0259] a monocyclic or bicyclic 4- to 15-membered heterocyclyl, which isas defined above;

[0260] —(C₁-C₃)-perfluoroalkylene, —(C₁-C₃)-alkylene-S(O)—(C₁-C₄)-alkyl,

[0261] —(C₁-C₃)-alkylene-S(O)₂-(C₁-C₃)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—N(R^(4′))—R^(5′),

[0262] —(C₁-C₃)-alkylene-O—(C₁-C₄)-alkyl,—(C₀-C₃)-alkylene-(C₃-C₈)-cycloalkyl, or

[0263] —(C₀-C₃)-alkylene-het, wherein het is a residue selected out ofthe group azepine, azetidine, aziridine, azirine, 1,4-diazapane,1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine,dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan,imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine,isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline,ketopiperazine, morpholine, 1,4-oxazepane, 1,2-oxa-thiepane,1,2-oxathiolane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole,oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole,pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole,pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine,tetrazole, thiadiazine thiadiazole, 1,2-thiazine, 1,3-thiazirie,1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl,thietan, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, wherein het isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14,

[0264] R^(4′) and R^(5′) are independent of one another are identical ordifferent and are hydrogen or —(C₁-C₄)-alkyl,

[0265] R² is a direct bond or —(C₁-C₄)-alkylene, or

[0266] R¹ and R3 together with the atoms to which they are bonded canform a 6- to 8-membered cyclic residue selected out of the groupazocane, azocane-2-one, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine,[1,4]diazocane, [1,2]diazocan-3-one, [1,3]diazocan-2-one, dioxazine,[1,4]dioxocane, dioxole, ketopiperazine, morpholine, 1,2-oxazine,1,3-oxazine, 1,4-oxazine, [oxocane, oxocan-2-one, piperazine,piperidine, pyran, pyrazine, pyridazine, pyrimidine or5,6,7,8-tetrahydro-1H-azocin-2-one, wherein said cyclic group isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14, or

[0267] R¹—N—R²—V can form a 4- to 8-membered cyclic group selected outof the group azepine, azetidine, dioxazole, dioxazine, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine,isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline,isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, oxazole,piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole,thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole,wherein said cyclic group is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14,

[0268] R14 is fluorine, chlorine, bromine, iodine, —OH, ═O,—(C₁-C₈)-alkyl, —(C₁-C₄)-alkoxy, —NO₂, —C(O)—OH, —CN, —NH₂,—C(O)—O—(C₁-C₄)-alkyl, —(C₀-C₈)-alkyl-SO₂—(C₁-C₄)-alkyl,—(C₀-C₈)-alkyl-SO₂—(C₁-C₃)-perfluoroalkyl,—(C₀-C₈)-alkyl-SO₂—N(R¹⁸)—R²¹, —C(O)—NH—(C₁-C₈)-alkyl,—C(O)—N—[(C₁-C₈)-alkyl]₂, —NR¹⁸—C(O)—NH—(C₁-C₈)-alkyl,

[0269] —C(O)—NH₂, —S—R¹⁸, or —NR¹⁸—C(O)—NH—[(C₁-C₈)-alkyl]₂,

[0270] wherein R¹⁸ and R²¹ are independently from each other hydrogen,—(C₁-C₃)-perfluoroalkyl or —(C₁-C₆)-alkyl,

[0271] V is 1) a monocyclic or bicyclic 6- to 14-membered aryl out ofthe group phenyl, naphthyl, biphenylyl, anthryl or fluorenyl, whereinaryl is mono-, di- or trisubstituted independently of one another byR14,

[0272] 2) a heterocyclyl out of the group acridinyl, azaindole(1H-pyrrolopyridine), azabenzimidazolyl, azaspirodecanyl, azepinyl,azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl,4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl,decahydrochinolinyl, 1,4-diazepane, 4,5-dihydrooxa-zolinyl, dioxazolyl,dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl,imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl,isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl,isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl,naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,2-oxazinyl,1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl,phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl,4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl,tetrahydroisochinolinyl, tetrahydrochinolinyl,1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl,1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl and xanthenyl,

[0273] wherein said heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14,

[0274] G is a direct bond, —(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—,—(CH₂)_(m)—CH(OH)—(CH₂)_(n)—, —(CH₂)_(m)—, —(CH₂)_(m)—O—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—(CH₂)_(n)—, —(CH₂)—S—(CH₂)_(n)—,—(CH₂)_(m)—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—, —(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)— or—(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—,

[0275] n and m are independently of one another identical or differentand are the integers zero, 1, 2, 3, 4, 5 or 6,

[0276] M is 1) hydrogen,

[0277] 2) —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R14,

[0278] 3) —C(O)—N(R¹¹)—R¹²,

[0279] 4) —(CH₂)_(m)—NR¹⁰,

[0280] 5) —(C₆-C₁₄)-aryl, wherein aryl is as defined above and whereinaryl is unsubstituted or mono-, di- or trisubstituted independently ofone another by R14,

[0281] 6) —(C₄-C₁₅)-heterocyclyl, wherein heterocyclyl is as definedabove and is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R14, or

[0282] 7) —(C₃-C₈)-cycloalkyl, wherein said cycloalkyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R14,

[0283] R3 is 1) hydrogen,

[0284] 2) halogen,

[0285] 3) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0286] 4) —(C₁-C₃)-perfluoroalkyl,

[0287] 5) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0288] 6) —(C₀-C₄)-alkylene-O—R¹⁹, wherein R19 is

[0289] a) hydrogen,

[0290] b) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or tri substituted independently of one another by R13,

[0291] c) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0292] d) —CF₃,

[0293] e) —CHF₂,

[0294] 7) —NO₂,

[0295] 8) —CN,

[0296] 9) —SO_(s)—R¹¹, wherein s is 1 or 2,

[0297] 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2,

[0298] 11) —(C₀-C₄)-alkylene-C(O)—R¹¹,

[0299] 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹,

[0300] 13) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹²,

[0301] 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹²,

[0302] 15) —NR¹⁰—SO₂—R¹⁰,

[0303] 16) —S—R¹⁰,

[0304] 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl,

[0305] 18) —C(O)—O—C(R15, R16)—O—C(O)—R17,

[0306] 19)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl,

[0307] 20) —C(O)—O—C(R15, R16)—O—C(O)—O—R17,

[0308] 21) —(C₀-C₄)-alkylene-(C₆-C₁₄)-aryl, wherein aryl is mono-, di-or trisubstituted independently of one another by R13,

[0309] 22) —(C₀-C₄)-alkylene-(C₄-C₁₅)-heterocyclyl, wherein heterocyclylis unsubstituted or mono-, di- or trisubstituted independently of oneanother by R13

[0310] 23) —(C₀-C₄)-aikylene-(C₃-C₈)-cycloalkyl, wherein cycloalkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13,

[0311] 24) —(C₀-C₄)-alylene-het, wherein het is unsubstituted or mono-,di- or trisubstituted independently of one another by R13,

[0312] 25)—(C₀-C₃)-alkylene-O—CH₂—(C₁-C₃)-perfluoroalkylene-CH₂—O—(C₀-C₃)-alkyl,

[0313] 26) —SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2,

[0314] 27) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³,

[0315] 28) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or

[0316] 29) a residue from the following list

[0317] where Me is methyl, or if two —OR19 residues are attached toadjacent atoms they can form together with the atoms which they areattached to a 1,3-dioxole ring or a 2,3-dihydro-[1,4]dioxine ring, whichis substituted one, two, three or four times by R13,

[0318] R11and R12 are independently of one another identical ordifferent and are

[0319] 1) hydrogen,

[0320] 2) —(C₀-C₆)-alkyl, wher ein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0321] 3) —(C₀-C₆)-alkyl-(C₃-C₈)-cycloalkyl,

[0322] 4) —SO_(t)—R¹⁰, wherein t is 1 or 2,

[0323] 5) —(C₀-C₆)-alkyl-(C₆-C₁₄)-aryl, wherein alkyl and arylindependently from one another are unsubstituted or mono-, di- or trisubstituted by R13,

[0324] 6) —(C₁-C₃)-perfluoroalkyl,

[0325] 7) —O—R¹⁷, or

[0326] 8) —(C₀-C₆)-alkyl-(C₄-C₁₅)-heterocyclyl, wherein alkyl andheterocyclyl are as defined above and are independently from one anotherunsubstituted or mono-, di- or trisubstituted by R13, or

[0327] R11and R12 together with the nitrogen atom to which they arebonded form a heterocyclic ring out of the group azepine, azetidine,dioxazole, dioxazine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole,isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine,2-isoxazoline, ketopiperazine, morpholine, [1,4]oxazepane, oxazole,piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole,thiadiazole, thiazolidine, thiazoline, thiomorpholine, thiophene,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or1,2,4-triazole, wherein said heterocyclic ring is unsubstituted ormono-, di- or trisubstituted independently of one another by R13,

[0328] R13 is halogen, —NO₂, —CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰,—C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰, —(C₃-C₈)-cycloalkyl,—(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —N(R¹⁰)—S(O)_(u)—R¹⁰, wherein u is1 or 2, —S—R¹⁰, —SO_(r)—R¹⁰, wherein r is 1 or 2, —S(O)_(v)—N(R¹⁰)—R²⁰,wherein v is 1 or 2, —C(O)—R¹⁰, —(C₁-C₈)-alkyl, —(C₁-C₈)-alkoxy, phenyl,phenyloxy-, —O—CF₃, —(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—R¹⁷,—(C₁-C₄)-alkoxy-phenyl, —(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—O—R17,—(C₁-C₃)-perfluoroalkyl, —O—R15, —NH—C(O)—NH—R¹⁰, —NH—C(O)—O—R¹⁰, or aresidue from the following list

[0329] R¹⁰ and R²⁰ are independently of one another hydrogen,—(C₁-C₆)-alkyl, —(C₀-C₄)-alkyl-OH, —(C₀-C₄)-alkyl-O—(C₁-C₄)-alkyl or—(C₁-C₃)-perfluoroalkyl,

[0330] R15 and R16 are independently of one another hydrogen,—(C₁-C₆)-alkyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl,wherein each ring is unsubstituted or substituted one to three times byR¹⁰, and

[0331] R17 is —(C₁-C₆)-alkyl, —(C₁-C₆)-alkyl-OH,—(C₁-C₆)-alkyl-O—(C₁-C₆)-alkyl, —(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-O—(C₁-C₈)-alkyl-(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-(C₃-C₈)-cycloalkyl, wherein said cycloalkyl ring isunsubstituted or substituted one, two or three times by —OH,—O—(C₁-C₄)-alkyl or R¹⁰,

[0332] in all its stereoisomeric forms and mixtures thereof in anyratio, and its physiologically tolerable salts

[0333] Another particular embodiment of the present invention relates toa compound of formula I, wherein one of J₁ and J₂ is N, and the other isN—Q—R⁰,

[0334] R⁰ is 1) a monocyclic or bicyclic 6- to 14-membered aryl out ofthe group phenyl, naphthyl, biphenyl, anthryl or fluorenyl, wherein arylis mono-, di- or trisubstituted independently of one another by R8,

[0335] 2) a heterocyclyl out of the group benzimidazolyl,1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl,benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl,isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl,pteridinyl, purinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl,pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or1,4,5,6-tetrahydro-pyridazinyl, wherein said heterocyclyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R8, or

[0336] 3) a heterocyclyl out of the group azabenzimidazolyl,benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl, benzothiazolyl,benzothiophenyl, benzoxazolyl, chromanyl, cinnolinyl, 2-furyl, 3-furyl;imidazolyl, indolyl, indazolyl, isochromanyl, isoindolyl, isoquinolinyl,isothiazolyl, isoxazolyl, oxazolyl, phthalazinyl, pteridinyl, purinyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridoimidazolyl, pyridopyridinyl,pyridopyrimidinyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidinyl,pyrrolyl; 2-pyrrolyl, 3-pyrrolyl, quinolinyl, quinazolinyl,quinoxalinyl, tetrazolyl, thiazolyl, 2-thienyl or 3-thienyl,

[0337] which is additionally substituted by a heterocyclyl selected outof the group acridinyl, azabenzimidazolyl, azaspirodecanyl, azepinyl,azetidinyl, aziridinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, carbazolyl,4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl,decahydrochinolinyl, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl,1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl,imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl,isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl),isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl,isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl,morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl,1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl,oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl,4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl,tetrahydroisochinolinyl, tetrahydrochinolinyl,1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl,1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl and xanthenyl,

[0338] wherein heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8,

[0339] R8 is 1. F, Cl or Br,

[0340] 2. —NO₂,

[0341] 3. —CN,

[0342] 4. —C(O)—NH₂,

[0343] 5. —OH,

[0344] 6. —NH₂,

[0345] 7. —OCF₃

[0346] 8. a monocyclic or bicyclic 6- to 14-membered aryl, wherein arylis as defined above and is mono-, di- or trisubstituted independently ofone another by halogen or —O—(C₁-C₈)-alkyl,

[0347] 9. —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by halogen, NH₂, —OH or amethoxy residue, or

[0348] 10. —O—(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-,di- or trisubstituted independently of one another by halogen, NH₂, —OHor a methoxy residue,

[0349] 11. —SO₂CH₃ or

[0350] 12. —SO₂CF₃,

[0351] provided that R8 is at least one halogen, —C(O)—NH₂ or—O—(C₁-C₈)-alkyl residue, if R0 is a aryl or a heterocyclyl, which areas defined above,

[0352] substructure D is a residue selected out of the group phenyl,pyridyl, pyridyl-N-oxide pyridyl, pyrrolyl, furyl, thienyl, imidazolyl,pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, isothiazolyl,thiadiazolyl, pyrimidinyl, pyridazinyl, pyrazinyl and is unsubstitutedor substituted 1, 2, 3 or 4 times by R3,

[0353] Q is a direct bond, —(C₀-C₂)-alkylene-C(O)—NR¹⁰—,—NR¹⁰—C(O)—NR¹⁰—, —NR¹⁰—C(O)—, —SO₂—, —(C₁-C₆)-alkylene or—(C₀-C₃)-alkylene-C(O)—O—(C₀-C₂)-alkylene,

[0354] R¹ is hydrogen, —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted orsubstituted one to three times by R13; —(C₁-C₃)-alkylene-C(O)—NH—R⁰,—(C₁-C₃)-alkylene-C(O)—O—R15, —(C₁-C₃)-perfluoroalkylene,—(C₁-C₃)-alkylene-S(O)—(C₁-C₄)-alkyl,—(C₁-C₃)-alkylene-S(O)₂-(C₁-C₃)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—N(R^(4′))—R^(5′),—(C₁-C₃)-alkylene-O—(C₁-C₄)-alkyl, —(C₀-C₃)-alkylene-(C₃-C₈)-cycloalkyl,or —(C₀-C₃)-alkylene-het, wherein het is a residue selected out of thegroup azepine, azetidine, aziridine, azirine, 1,4-diazepane,1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine, diazirine,dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan,imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine,isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline,ketopiperazine, morpholine, 1,2-oxa-thiepane, 1,2-oxathiolane,1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole,oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine, pyrazole,pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole,pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine,tetrazole, thiadiazine thiadiazole, 1,2-thiazine, 1,3-thiazine,1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine, thiazoline, thienyl,thietan, thiomorpholine, thiopyran, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, wherein het isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14,

[0355] R^(4′) and R^(5′) are independent of one another are identical ordifferent and are hydrogen or —(C₁-C₄)-alkyl,

[0356] R² is a direct bond or -C₁-C₄)-alkylene, or

[0357] R¹ —N—R²—V form a 4- to 8-membered cyclic group selected out ofthe group azepine, azetidine, 1,4-diazepane, dioxazole, dioxazine,1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline,imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole,isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine,1,4-oxazepane, oxazole, piperazine, piperidine, pyrazine, pyrazole,pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole,pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine,tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline,thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole or 1,2,4-triazole, wherein said cyclic group isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14,

[0358] R14 is fluorine, chlorine, bromine, iodine, —OH, ═O,—(C₁-C₈)-alkyl, —(C₁-C₄)-alkoxy, —NO₂, —C(O)—OH, —CN, —NH₂,—C(O)—O—(C₁-C₄)-alkyl, —(C₀-C₈)-alkyl-SO₂—(C₁-C₄)-alkyl,—(C₀-C₈)-alkyl-SO₂-(C₁-C₃)-perfluoroalkyl,—(C₀-C₈)-alkyl-SO₂—N(R¹⁸)—R²¹, —C(O)—NH—(C₁-C₈)-alkyl,—C(O)—N—[(C₁-C₈)-alkyl]₂, —NR¹⁸—C(O)—NH—(C₁-C₈)-alkyl, —C(O)—NH₂,—S—R¹⁸, or —NR¹⁸—C(O)—NH—[(C₁-C₈)-alkyl]₂,

[0359] wherein R¹⁸ and R²¹ are independently from each other hydrogen,—(C₁-C₃)-perfluoroalkyl or —(C₁-C₆)-alkyl,

[0360] V is 1) a het residue out of the group azaindole(1H-pyrrolopyridine), azepine, azetidine, aziridine, azirine,1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine,diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane,furan, imidazole, imidazoline, imidazolidine, isothiazole,isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine,2-isoxazoline, ketopiperazine, morpholine, 1,2-oxa-thiepane,1,2-oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine,oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine,pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine,pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine,tetrazine, tetrazole, thiadiazine, thiadiazole, 1,2-thiazine,1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine,thiazoline, thienyl, thietan, thiomorpholine, thiopyran, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, whichis as defined above and wherein het is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14, or

[0361] 2) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14,

[0362] G is a direct bond, —(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—,—(CH₂)_(m)—CH(OH)—(CH₂)_(n)—, —(CH₂)_(m)—, —(CH₂)_(m)—O—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—(CH₂)_(n)—, —(CH₂)—S—(CH₂)_(n)—,—(CH₂)_(m)—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—, —(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)— or—(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—,

[0363] n and m are independently of one another identical or differentand are the integers zero, 1, 2, 3, 4, 5 or 6,

[0364] M is 1) hydrogen,

[0365] 2) —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R14,

[0366] 3) —C(O)—N(R11)—R¹²,

[0367] 4) —(CH₂)_(m)—NR¹⁰,

[0368] 5) phenyl or naphthyl, wherein phenyl or naphthyl areunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14,

[0369] 6) heterocyclyl, wherein heterocyclyl is a residue out of thegroup which can be derived from azepane, azepine, 1,4-diazepane,1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, isothiazole,isoxazole, isoxazolidine, 2-isoxazoline, ketomorpholine, ketopiperazine,morpholine, oxazole, [1,4]-oxazepane, piperazine, piperazinone,piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine,pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran,1,4,5,6-tetrahydro-pyridazinyl, tetrazine, tetrazole, thiadiazole,thiazole, thiophene, thiomorpholine, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, wherein saidheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14, or

[0370] 7) —(C₃-C₈)-cycloalkyl, wherein said cycloalkyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R14,

[0371] R3 is 1) hydrogen,

[0372] 2) halogen,

[0373] 3) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0374] 4) —(C₁-C₃)-perfluoroalkyl,

[0375] 5) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0376] 6) —(C₀-C₄)-alkylene-O—R19, wherein R19 is

[0377] a) hydrogen,

[0378] b) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0379] c) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0380] d) —CF₃, or

[0381] e) CHF₂,

[0382] 7) —CN,

[0383] 8) —(C₀-C₄)-aikylene-(C₄-C₁₅)-heterocyclyl, wherein heterocyclylis as defined above and is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R13,

[0384] 9) —SO_(s)—R¹¹, wherein s is 1 or 2,

[0385] 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2,

[0386] 11) —(C₀-C₄)-alkylene-C(O)—R¹¹,

[0387] 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹,

[0388] 13) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R12,

[0389] 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹²,

[0390] 15) —NR¹⁰—SO₂—R¹⁰,

[0391] 16) —(C₀-C₄)-alkylene-het, wherein het is as defined above and isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13,

[0392] 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl,

[0393] 18) —C(O)—O—C(R15, R16)—O—C(O)—R17,

[0394] 19)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl,

[0395] 20) —C(O)—O—C(R15, R16)—O—C(O)—O—R17,

[0396] 21) —(C₀-C₄)-alkylene-(C₆-C₁₄)-aryl, wherein aryl is as definedabove and is mono-, di- or trisubstituted independently of one anotherby R13,

[0397] 22) —(C₀-C₄)-alkylene-(C₃-C₈)-cycloalkyl, wherein cycloalkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13,

[0398] 23) —(C₀-C₃)-alkylene-O—CH₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,

[0399] 24) —(C₀-C₃)-alkylene-O—CH₂—CF₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,

[0400] 25) —(C₀-C₃)-aikylene-O—CH₂—(C₁-C₃)-perfluoroalkylene-CH₂—OH,

[0401] 26) —SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2,

[0402] 27) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³,

[0403] 28) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or

[0404] 29) a residue from the following list

[0405] where Me is methyl, if two —OR19 residues are attached toadjacent atoms they can form together with the atoms which they areattached to a 1,3-dioxole ring or a 2,3-dihydro-[1,4]dioxine ring, whichis substituted one, two, three or four times by R13,

[0406] R11 and R12 are independently of one another identical ordifferent and are

[0407] 1) hydrogen,

[0408] 2) —(C₁-C₆)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0409] 3) —(C₀-C₆)-alkyl-(C₆-C₁₄)-aryl, wherein aryl is as defined aboveand wherein alkyl and aryl are independently from one anotherunsubstituted or mono-, di- or trisubstituted by R13,

[0410] 4) —O—R¹⁷, or

[0411] 5) —(C₀-C₆)-alkyl-(C₄-C₁₅)-heterocyclyl, wherein alkyl andheterocyclyl is as defined above and independently from one another areunsubstituted or mono-, di- or trisubstituted by R13, or

[0412] R¹¹ and R12 together with the nitrogen atom to which they arebonded can form a ring selected out of the group azepine, azetidine,1,4-diazepane, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole,isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine,2-isoxazoline, ketopiperazine, morpholine, [1,4]oxazepane, oxazole,piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole,thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, whichis unsubstituted or mono-, di- or trisubstituted independently of oneanother by R13,

[0413] R13 is fluorine, chlorine, bromine, iodine, —NO₂, —CN, ═O, —OH,—CF₃, —C(O)—O—R¹⁰, —C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰,—(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —N(R¹⁰)—S(O)₂—R¹⁰, —S—R¹⁰,—SO₂—R¹⁰, —S(O)₂—N(R¹⁰)—R²⁰, —C(O)—R¹⁰, —(C₁-C₈)-alkyl, —(C₁-C₈)-alkoxy,phenyl, phenyloxy-, —O—CF₃, —(C₁-C₃)-perfluoroalkyl,—(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—R¹⁷, —(C₁-C₄)-alkoxy-phenyl,—(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—O—R¹⁷, —O—R¹⁵, —NH—C(O)—NH—R¹⁰,—NH—C(O)—O—R¹⁰, or a residue from the following list

[0414] R¹⁰ and R²⁰ are independently of one another hydrogen,—(C₁-C₆)-alkyl, —(C₀-C₄)-alkyl-OH, —(C₀-C₄)-alkyl-O—(C₁-C₄)-alkyl or—(C₁-C₃)-perfluoroalkl,

[0415] R15 and R16 are independently of one another hydrogen,—(C₁-C₆)-alkyl, or together form a ring out of the group cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring isunsubstituted or substituted one to three times by R¹⁰, and

[0416] R17 is —(C₁-C₆)-alkyl, —(C₁-C₆)-alkyl-OH,—(C₁-C₆)-alkyl-O—(C₁-C₆)-alkyl, —(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-O—(C₁-C₈)-alkyl-(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-(C₃-C₈)-cycloalkyl, wherein said cycloalkyl ring isunsubstituted or substituted one, two or three times by —OH,—O—(C₁-C₄)-alkyl or R¹⁰,

[0417] in all its stereoisomeric forms and mixtures thereof in anyratio, and its physiologically tolerable salts.

[0418] Another particular embodiment of the present invention relates toa compounds of formula I, wherein one of J₁ and J₂ is N, and the otheris N—Q—R⁰,

[0419] R0 is 1) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8,

[0420] 2) a heterocyclyl out of the group benzimidazolyl,1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzothiazolyl,benzothiophenyl, cinnolinyl, chromanyl, indazolyl, indolyl,isochromanyl, isoindolyl, isoquinolinyl, phenylpyridyl, phthalazinyl,pteridinyl, purinyl, pyridyl, pyridoimidazolyl, pyridopyridinyl,pyridopyrimidinyl, pyrimidinyl, quinazolinyl, quinolyl, quinoxalinyl or1,4,5,6-tetrahydro-pyridazinyl, wherein said heterocyclyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R8, or

[0421] 3) a heterocyclyl out of the group pyridyl, 2-pyridyl, 3-pyridyl,4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl;thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl,isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl,tetrazolyl, pyridazinyl and pyrazinyl, wherein said heterocyclyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R8, and in addition is substituted by a residue selected outof the group pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl,2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl,3-thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl,thiadiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridazinyl andpyrazinyl, wherein said residue is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8

[0422] R8 is 1. F, Cl, Br or J,

[0423] 2. —C(O)—NH₂,

[0424] 3. —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by halogen, —OH or amethoxy residue, or

[0425] 4. —O—(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by halogen or a methoxyresidue, provided that R8 is at least one halogen, —C(O)—NH₂ or—O—(C₁-C₈)-alkyl residue, if R0 is a aryl or a heterocyclyl, which areas defined above,

[0426] substructure D is a residue selected out of the group phenyl,pyridyl, pyridyl-N-oxide, pyrrolyl, furyl, thienyl, imidazolyl,pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, isothiazolyl,thiadiazolyl, pyrimidinyl, pyridazinyl, pyrazinyl and is unsubstitutedor substituted 1, 2, 3 or 4 times by R3,

[0427] Q is a direct bond, —C(O)—; —SO₂— or —(C₁-C₆)-alkylene,—(C₀-C₂)-alkylene-C(O)—NR¹⁰— or—(C₀-C₃)-alkylene-C(O)—O—(C₀-C₂)-alkylene,

[0428] R¹ is hydrogen, —(C₁-C₂)-alkyl, —(C₁-C₃)-alkylene-C(O)—NH—R0,—(C₁-C₃)-perfluoroalkylene, —(C₁-C₃)-alkylene-C(O)—O—R¹⁵,—(C₁-C₃)-alkylene-S(O)₂—(C₁-C₃)-alkyl or—(C₁-C₃)-alkylene-S(O)₂—N(R^(4′))—R^(5′), wherein R^(4′) and R^(5′) areindependent of one another are identical or different and are hydrogenor —(C₁-C₄)-alkyl,

[0429] R² is a direct bond or —(C₁-C₂)-alkylene,

[0430] R¹—N—R²—V can form a 4- to 7-membered cyclic group out of thegroup azetidine, azetidinone, piperidine, piperazine, pyridine,pyrimidine, pyrrolidine, pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole,1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, azepine,ketopiperazine, 1,4-oxazepane, oxazole, isoxazole, isoxazolidine,2-isoxazoline, morpholine, thiazole, isothiazole, thiadiazole orthiomorpholine, wherein said cyclic group is unsubstituted or mono-, di-or trisubstituted independently of one another by R14,

[0431] R14 is fluorine, chlorine, —OH, ═O, —(C₁-C₈)-alkyl, —C(O)—OH,—CN, —NH₂, —C(O)—O—(C₁-C₄)-alkyl, —C(O)—NH—(C₁-C₈)-alkyl,—C(O)—N—[(C₁-C₈)-alkyl]₂, —C(O)—NH₂ or —N(R¹⁸)—R²¹, wherein R¹⁸ and R²¹are independently from each other hydrogen, —(C₁-C₃)-perfluoroalkyl or—(C₁-C₄)-alkyl,

[0432] V is 1. a cyclic residue out of the group containing compoundswhich are derived from azaindole (1H-pyrrolopyridine), aziridine,azirine, azetidine, azetidinone, 1,4-diazepane, pyrrole, pyrrolidine,pyridonyl, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole,tetrazole, pyridine, pyrimidine, pyrazine, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, tetrazine, tetrazole, azepine,diazirine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, pyridazine,piperidine, piperazine, pyrrolidinone, ketopiperazine, furan, pyran,dioxole, 1,4-oxazepane, oxazole, isoxazole, 2-isoxazoline,isoxazolidine, morpholine, oxirane, oxaziridine, 1,3-dioxolene,1,3-dioxolane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxaziridine,thiophene, thiopyran, thietan, thiazole, isothiazole, isothiazoline,isothiazolidine, 1,2-oxathiolan, thiodiazole, thiopyran, 1,2-thiazine,1,3-thiazole, 1,3-thiazine, 1,4-thiazine, thiadiazine or thiomorpholine,wherein said cyclic residue is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14, or

[0433] 2. phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14, or

[0434] G is a direct bond, —(CH₂)_(m)—, or —(CH₂)_(m)—NR¹⁰—,

[0435] m is the integers zero, 1, 2, 3 or 4,

[0436] M is 1. hydrogen,

[0437] 2. heterocyclyl, wherein heterocyclyl is a residue out of thegroup which can be derived from azepane, azepine, 1,4-diazepane,1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, isothiazole,isoxazole, isoxazolidine, 2-isoxazoline, ketomorpholine, ketopiperazine,morpholine, oxazole, [1,4]-oxazepane, piperazine, piperazinone,piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine,pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran,1,4,5,6-tetrahydro-pyridazinyl, tetrazine, tetrazole, thiadiazole,thiazole, thiomorpholine, thiophene, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, wherein saidheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14,

[0438] 3. —(C₁-C₆)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R14, or

[0439] 4. (C₃-C₆)-cycloalkyl,

[0440] 5. —C(O)—N(R¹¹)—R¹²,

[0441] R3 is 1) hydrogen,

[0442] 2) halogen,

[0443] 3) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0444] 4) —(C₁-C₃)-perfluoroalkyl,

[0445] 5) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0446] 6) —(C₀-C₄)-alkylene-O—R19, wherein R19 is

[0447] a) hydrogen,

[0448] b) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0449] c) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0450] d) —CF₃, or

[0451] e) CHF₂,

[0452] 7) —CN,

[0453] 8) —NR¹⁰—SO₂—R¹⁰,

[0454] 9) —SO_(s)—R¹¹, wherein s is 1 or 2,

[0455] 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2,

[0456] 11) —(C₀-C₄)-alkylene-C(O)—R¹¹,

[0457] 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹,

[0458] 13) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹²,

[0459] 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹²,

[0460] 15)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl,

[0461] 16) —C(O)—O—C(R15, R16)—O—C(O)—R17,

[0462] 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl,

[0463] 18) —C(O)—O—C(R15, R16)—O—C(O)—O—R17,

[0464] 20) —(C₀-C₃)-alkylene-O—CH₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,

[0465] 21) —(C₀-C₃)-alkylene-O—CH₂—CF₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,

[0466] 22) —(C₀-C₃)-alkylene-O—CH₂—(C₁-C₃)-perfluoroalkylene-CH₂—OH,

[0467] 23) —SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2,

[0468] 24) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³,

[0469] 25) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or

[0470] 26) a residue from the following list

[0471]  wherein Me is methyl,

[0472] if two —OR19 residues are attached to adjacent atoms they canform together with the atoms which they are attached to a 1,3-dioxolering or a 2,3-dihydro-[1,4]dioxine ring, which is substituted one, two,three or four times by R13,

[0473] R¹¹and R¹² together with the nitrogen atom to which they arebonded can form a ring selected out of the group azepine, azetidine,1,4-diazepane, dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, imidazole, imidazoline, imidazolidine, isothiazole,isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine,2-isoxazoline, ketopiperazine, morpholine, [1,4]-oxazepane, oxazole,piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole,thiadiazole, thiazolidine, thiazoline, thiomorpholine, thiophene,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or1,2,4-triazole, wherein said ring is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0474] R13 is fluorine, chlorine, —NO₂, —CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰,—C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰, —(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃,—N(R¹⁰)—S(O)₂—R¹⁰, —S—R¹⁰, —SO₂—R¹⁰, —S(O)₂—N(R¹⁰)—R²⁰, —C(O)—R¹⁰,—(C₁-C₈)-alkyl, —(C₁-C₈)-alkoxy, phenyl, phenyloxy-, —O—CF₃,—(C₁-C₃)-perfluoroalkyl, —NH—C(O)—NH—R¹⁰, —(C₀-C₄)-alkyl-C(O)—O—C(R15,R16)—O—C(O)—R17, —(C₁-C₄)-alkoxy-phenyl,—(C₀-C₄)-alkyl-C(O)—O—C(R15,R16)—O—C(O)—O—R17, —O—R15, —NH—C(O)—O—R¹⁰,or a residue from the following list

[0475] wherein Me is methyl, R¹⁰ and R²⁰ are independently of oneanother hydrogen, —(C₁-C₆)-alkyl, —(C₀-C₄)-alkyl-OH,—(C₀-C₄)-alkyl-O—(C₁-C₄)-alkyl or —(C₁-C₃)-perfluoroalkyl,

[0476] R15 and R16 are independently of one another hydrogen,—(C₁-C₆)-alkyl, or together form a ring out of the group cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring isunsubstituted or substituted one to three times by R¹⁰, and

[0477] R17 is —(C₁-C₆)-alkyl, —(C₁-C₆)-alkyl-OH,—(C₁-C₆)-alkyl-O—(C₁-C₆)-alkyl, —(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-O—(C₁-C₈)-alkyl-(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-(C₃-C₈)-cycloalkyl, wherein said cycloalkyl ring isunsubstituted or substituted one, two or three times by —OH,—O—(C₁-C₄)-alkyl or R¹⁰,

[0478] in all its stereoisomeric forms and mixtures thereof in anyratio, and its physiologically tolerable salts.

[0479] Another particular embodiment of the present invention relates toa compound of formula I, wherein one of J₁ and J₂ is N, and the other isN—Q—R⁰,

[0480] R0 is 1) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8,

[0481]2) a heterocyclyl selected out of the group indolyl, isoindolyl,benzofuranyl, benzothiophenyl, 1,3-benzodioxolyl, indazolyl,benzimidazolyl, benzoxazolyl, benzothiazolyl, quinolinyl, isoquinolinyl,chromanyl, isochromanyl, cinnolinyl, quinazolinyl, quinoxalinyl,phthalazinyl, pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl,pyridyl, purinyl and pteridinyl, wherein said heterocyclyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R8,

[0482] 3) a heterocyclyl out of the group pyridyl, 2-pyridyl, 3-pyridyl,4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, furyl, 2-furyl, 3-furyl;thienyl, 2-thienyl, 3-thienyl, imidazolyl, pyrazolyl, oxazolyl,isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, triazolyl,tetrazolyl, pyridazinyl and pyrazinyl, wherein said heterocyclyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R8,

[0483] and in addition is substituted by a residue selected out of thegroup pyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl,3-pyrrolyl, fuiryl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl,imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl,isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, whereinsaid residue is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R8

[0484] R8 is 1. is F, Cl, Br, J,

[0485] 2. —C(O)—NH₂,

[0486] 3. —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by halogen, —OH or amethoxy residue, or

[0487] 4. —O—(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by halogen or a methoxyresidue,

[0488] provided that R8 is at least one halogen, —C(O)—NH₂ or—O—(C₁-C₈)-alkyl residue, if R0 is a aryl or a heterocyclyl, which areas defined above,

[0489] substructure D is a residue selected out of the group phenyl,pyridyl, pyridyl-N-oxide, pyrrolyl, furyl, thienyl, imidazolyl,pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, isothiazolyl,thiadiazolyl, pyrimidinyl, pyridazinyl, pyrazinyl and is unsubstitutedor substituted 1, 2, 3 or 4 times by R³,

[0490] Q is a direct bond, —C(O)—; —SO₂—, —C(O)—O-methylene,—(C₁-C₆)-alkylene or —(C₀-C₂)-alkylene-C(O)—NR¹⁰—,

[0491] R¹ is hydrogen or —(C₁-C₂)-alkyl,

[0492] R² is a direct bond or —(C₁-C₂)-alkylene, or

[0493] R¹—N—R²—V can form a 4- to 7-membered cyclic group out of thegroup piperidine, piperazine, pyridine, pyrimidine, pyrrolidine,pyrrolidinone, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole, 1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, oxazole,isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole,isothiazole, thiadiazole or thiomorpholine, wherein said cyclic group isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14,

[0494] R14 is fluoro, chlorine, —(C₁-C₄)-alkyl or —NH₂,

[0495] V is 1. a cyclic residue out of the group containing compounds,which are derived from azaindolyl (1H-pyrrolopyridyl), azetidine,azepine, aziridine, azirine, 1,4-diazepane, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, diazirine, 1,3-dioxolane, dioxazole,furan, imidazole, isoquinoline, isothiazole, isothiazolidine,isothiazoline, isoxazole, 2-isoxazoline, isoxazolidine, ketopiperazine,morpholine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole,1,2-oxathiolan, piperidine, pyran, pyrazine, pyrazole, pyridazine,piperazine, pyridine, pyridone, pyrimidine, pyrrole, pyrrolidine,pyrrolidinone, quinazoline, quinoline, tetrazine, tetrazole,thiadiazine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole,thietan, thiomorpholine, thiophene, thiopyran, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole,

[0496] wherein said cyclic residue is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14, or

[0497] 2. phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14,

[0498] G is a direct bond, —(CH₂)_(m)—, or —(CH₂)_(m)—NR¹⁰—,

[0499] m is the integers zero, 1, 2, 3 or 4,

[0500] M is 1. hydrogen,

[0501] 2. heterocyclyl, wherein heterocyclyl is a residue out of thegroup which can be derived from 1,4-diazepane, ketomorpholine,thiophene, pyridazone, piperidine, piperazine, pyridine, pyrimidine,pyrrolidine, pyrrolidinone, pyridonyl, imidazole, pyridazine, pyrazine,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole,1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole,isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole,tetrahydropyran, 1,4,5,6-tetrahydro-pyridazinyl, thiadiazole orthiomorpholine, wherein said heterocyclyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R14,

[0502] 3. —(C₁-C₆)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R14, or

[0503] 4. (C₃-C₆)-cycloalkyl,

[0504] R3 is 1) hydrogen,

[0505] 2) halogen,

[0506] 3) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0507] 4) —(C₁-C₃)-perfluoroalkyl,

[0508] 5) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0509]6) —(C₀-C₄)-alkylene-O—R19, wherein R19 is

[0510] a) hydrogen,

[0511] b) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13, or

[0512] c) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0513] d) —CF₃, or

[0514] e) —CHF₂,

[0515] 7) —CN,

[0516] 8) —NR¹⁰—SO₂—R¹⁰,

[0517] 9) —SO_(s)—R¹¹, wherein s is 1 or 2,

[0518] 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2,

[0519] 11) —(C₀-C₄)-alkylene-C(O)—R¹¹,

[0520] 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹,

[0521] 13) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹²,

[0522] 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹²,

[0523] 15)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl,

[0524] 16) —C(O)—O—C(R15, R16)—O—C(O)—R17,

[0525] 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl,

[0526] 18) —C(O)—O—C(R15, R16)—O—C(O)—O—R17,

[0527] 19) —(C₀-C₃)-alkylene-O—CH₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,

[0528] 20) —(C₀-C₃)-alkylene-O—CH₂—CF₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,

[0529] 21) —(C₀-C₃)-alkylene-O—CH₂—(C₁-C₃)-perfluoroalkylene-CH₂—OH,

[0530] 22) —SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2,

[0531] 23) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³,

[0532] 24) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or

[0533] 25) a residue from the following list

[0534]  wherein Me is methyl,

[0535] R11 and R12 are independently of one another identical ordifferent and are

[0536] 1) hydrogen,

[0537] 2) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0538] 3) —(C₀-C₆)-alkyl-(C₃-C₆)-cycloalkyl,

[0539] 4) —O—R¹⁷, or

[0540] 5) —(C₀-C₆)-alkyl-(C₄-C₁₅)-heterocyclyl, wherein alkyl andheterocyclyl independently from one another are unsubstituted or mono-,di- or trisubstituted by R13 and wherein heterocyclyl is selected out ofthe group azetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole,imidazolidine, morpholine, (1,4)-oxazepane, oxazolidine, piperidine,piperazine, pyrrolidine, tetrahydrothiophene, thiazolidine orthiomorpholine, or

[0541] R11and R12 together with the nitrogen atom to which they arebonded form a heterocyclic ring, which is selected out of the groupazetidine, cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine,morpholine, (1,4)-oxazepane, oxazolidine, piperidine, piperazine,pyrrolidine, tetrahydrothiophene, thiazolidine or thiomorpholine,

[0542] R13 is fluorine, —CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰,—C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰, —(C₃-C₆)-cycloalkyl,—(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —S—R¹⁰, —SO₂—R¹⁰,—(C₁-C₃)-perfluoroalkyl, or a residue from the following list

[0543]  methyl,

[0544] R¹⁰ and R²⁰ are independently of one another hydrogen,—(C₁-C₄)-alkyl or —(C₁-C₃)-perfluoroalkyl,

[0545] R¹⁵ and R¹⁶ are independently of one another hydrogen,—(C₁-C₄)-alkyl, or together form a ring out of the group cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring isunsubstituted or substituted one to three times by R¹⁰, and

[0546] R17 is —(C₁-C₆)-alkyl, —(C₁-C₆)-alkyl-OH,—(C₁-C₆)-alkyl-O—(C₁-C₆)-alkyl, —(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-O—(C₁-C₈)-alkyl—(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-(C₃-C₈)-cycloalkyl, wherein said cycloalkyl ring isunsubstituted or substituted one, two or three times by —OH,—O—(C₁-C₄)-alkyl or R¹⁰,

[0547] in all its stereoisomeric forms and mixtures thereof in anyratio, and its physiologically tolerable salts.

[0548] Another particular embodiment of the present invention relates toa compound of formula I, wherein

[0549] R0 is 1. phenyl, wherein phenyl is unsubstituted or mono- ordisubstituted independently of one another by R8,

[0550] 2. pyridyl, wherein pyridyl is unsubstituted or mono- ordisubstituted independently of one another by R8, or

[0551] 3. a heterocyclyl out of the group thienyl, thiadiazolyl,isoxazolyl and thiazolyl, wherein said heterocyclyl is substituted by aresidue selected out of the group thienyl, 2-thienyl and 3-thienyl,wherein said residue is unsubstituted or mono- or disubstitutedindependently of one another by R8,

[0552] R8 is F, Cl, Br, —OCH₃, —C(O)—NH₂ or —O—CF₃,

[0553] substructure D is a residue selected out of the group phenyl,pyridyl, pyridyl-N-oxide, pyrrolyl, thienyl, imidazolyl, pyrazolyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl,pyrimidinyl, pyridazinyl or pyrazinyl and is unsubstituted orsubstituted 1, 2, 3 or 4 times by R3,

[0554] Q is a direct bond, —C(O)—; —SO₂—, —C(O)—O-methylene,—CH₂—C(O)—NH—, methylene or ethylene,

[0555] R¹ is hydrogen,

[0556] R² is a direct bond or methylene,

[0557] R¹—N—R²—V can form a 4- to 8-membered cyclic group out of thegroup azetidine, pyrrolidine, piperidine and piperazine,

[0558] R14 is fluorine, chlorine, methyl, ethyl, ═O, —SO₂—CH₃ or —NH₂,

[0559] V is 1. a residue out of the group containing compounds which isderived from azaindolyl (1H-pyrrolopyridyl), azetidine, 1,4-diazepane,isoxazole, isoquinoline, piperazine, piperidine, pyrazine, pyridazine,pyrimidine, pyrrolidine, quinazoline, quinoline or tetrahydropyrane,wherein said cyclic residue is unsubstituted or mono- or disubstitutedindependently of one another by R14, or

[0560] 2. phenyl, wherein phenyl is unsubstituted or mono- ordisubstituted independently of one another by R14,

[0561] G is a direct bond, —(CH₂)_(m)—, —C(O)— or —(CH₂)_(m)—NR¹⁰—,

[0562] m is the integers zero, 1 or 2,

[0563] M is hydrogen, (C₂-C₄)-alkyl, azepanyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, imidazolyl, ketomorpholinyl, morpholinyl,[1,4]Oxazepanyl, piperidinyl, piperidonyl, phenyl, pyrazinyl, pyrazolyl,pyridazinyl, pyridyl, pyrimidyl, pyrrolidinyl,1,4,5,6-tetrahydro-pyridazinyl, or tetrahydropyranyl, wherein theresidues are unsubstituted or mono- or disubstituted independently ofone another by R14

[0564] R3 is 1) hydrogen,

[0565] 2) fluorine, chlorine,

[0566] 3) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0567] 4) —(C₁-C₃)-perfluoroalkyl,

[0568] 5) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0569] 6) —(C₀-C₂)-alkylene-O—R¹⁹, wherein R19 is

[0570] a) hydrogen,

[0571] b) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0572] c) phenyl, wherein phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13,

[0573] d) —CF₃, or

[0574] e) —CHF₂,

[0575] 7) —CN,

[0576] 8) —NR¹⁰—SO₂—R¹⁰,

[0577] 9) —SO_(s)—R¹¹, wherein s is 1 or 2,

[0578] 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2,

[0579] 11) —(C₀-C₄)-alkylene-C(O)—R¹¹,

[0580] 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹,

[0581] 13) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹²,

[0582] 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹²,

[0583] 15)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl,

[0584] 16) —C(O)—O—C(R15, R16)—O—C(O)—R17,

[0585] 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl,

[0586] 18) —C(O)—O—C(R15, R16)—O—C(O)—O—R17,

[0587] 19) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³ or

[0588] 20) a residue from the following list

[0589]  wherein Me is methyl,

[0590] R11 and R12 are independently of one another identical ordifferent and are

[0591] 1) hydrogen,

[0592] 2) —(C₁-C₄)-alkyl, wherein alkyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R13,

[0593] 3) —(C₀-C₆)-alkyl-(C₃-C₆)-cycloalkyl,

[0594] 4) —O—R¹⁷, or

[0595] 5) —(C₀-C₆)-alkyl-heterocyclyl, wherein alkyl and heterocyclylindependently from one another are unsubstituted or mono-, di- ortrisubstituted by R13 and wherein heterocyclyl is selected out of thegroup azetidine, imidazolidine, 4,5-dihydro-[1,2,4]oxadiazole,-[1,3]dioxole, (1,4)-oxazepane or pyrrolidine or

[0596] R11and R12 together with the nitrogen atom to which they arebonded can form a ring, which is selected out of the group azetidine,imidazolidine, morpholine, (1,4)-oxazepane piperazine, piperidine,pyrrolidine or thiomorpholine,

[0597] R13 is fluorine, —CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰,—C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰, —(C₁-C₃)-alkyl, —(C₃-C₆)-cycloalkyl,—(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —S—R¹⁰, —SO₂—R¹⁰, —SO₂—NH,—(C₁-C₃)-perfluoroalkyl, or a residue from the following list

[0598]  wherein Me is methyl,

[0599] R¹⁰ and R²⁰ are independently of one another hydrogen,—(C₁-C₄)-alkyl or —(C₁-C₃)-perfluoroalkyl,

[0600] R¹⁵ and R¹⁶ are independently of one another hydrogen,—(C₁-C₄)-alkyl, or together form a ring out of the group cyclopropyl,cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring isunsubstituted or substituted one to three times by R¹⁰, and

[0601] R17 is —(C₁-C₆)-alkyl, —(C₁-C₆)-alkyl-OH,—(C₁-C₆)-alkyl-O—(C₁-C₆)-alkyl, —(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-O—(C₁-C₈)-alkyl-(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-(C₃-C₈)-cycloalkyl, wherein said cycloalkyl ring isunsubstituted or substituted one, two or three times by —OH,—O—(C₁-C₄)-alkyl or R¹⁰,

[0602] in all its stereoisomeric forms and mixtures thereof in anyratio, and its physiologically tolerable salts.

[0603] Another particular embodiment of the present invention relates toa compound of formula I, wherein J₁ is N, and J₂ is N—Q—R⁰.

[0604] Another particular embodiment of the present invention relates toa compound of formula I, wherein J₂ is N, and J₁ is N—Q—R⁰.

[0605] Another particular embodiment of the present invention relates toa compound of formula I, which is

[0606]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester,

[0607]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-6-carboxylicacid methyl ester,

[0608]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-7-carboxylicacid methyl ester,

[0609]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid,

[0610]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-7-carboxylicacid,

[0611]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-6-carboxylicacid,

[0612] Indazole-1,3-dicarboxylic acid1-[(5-chloro-pyridin-2-yl)-amide]-3-[(1-isopropyl-piperidin-4-yl)-amide],

[0613]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,

[0614]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 1-ethoxycarbonyloxy-ethyl ester,

[0615]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,

[0616]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,

[0617]5-(Azetidine-1-carbonyl)-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,

[0618]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-methanesulfonyl-ethyl)-amide],

[0619]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-sulfamoyl-ethyl)-amide],

[0620]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-morpholin-4-yl-ethyl)-amide],

[0621]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-trimethylsilanylmethyl-amide,

[0622]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[bis-(2-hydroxy-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],

[0623]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2-hydroxy-ethyl)-methyl-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],

[0624]{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-amino}-aceticacid ethyl ester,

[0625]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2,2-difluoro-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],

[0626]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-carbamoylmethyl-amide 3-[(1-isopropyl-piperidin-4-yl)-amide],

[0627]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-[(2-hydroxy-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],

[0628]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-{[2-(2-oxo-imidazolidin-1-yl)-ethyl]-amide},

[0629]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],

[0630]{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-amino}-aceticacid,

[0631]1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-(2S)-azetidine-2-carboxylicacid,

[0632]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2,2,2-trifluoro-ethyl)-amide],

[0633]{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-methyl-amino}-aceticacid,

[0634]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-hydroxy-ethyl ester,

[0635]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-([1,4]oxazepane-4-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,

[0636]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-hydroxy-azetidine-1-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,

[0637]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 3-[(1-isopropyl-piperidin-4-yl)-amide]5-(methoxy-amide),

[0638]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(piperidine-1-carbonyl)-phenyl]-amide,

[0639]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(pyrrolidine-1-carbonyl)-phenyl]-amide,

[0640]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(morpholine-4-carbonyl)-phenyl]-amide,

[0641]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(morpholine-4-carbonyl)-phenyl]-amide,

[0642]1-(1-{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carbonyl}-piperidin-4-yl)-pyrrolidin-2-one,

[0643]N-(5-Chloro-pyridin-2-yl)-2-{3-[4-(2-oxo-pyrrolidin-1-yl)-piperidine--carbonyl]-indazol-1-yl}-acetamide,

[0644]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide,

[0645]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide,

[0646]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (2′-methanesulfonyl-biphenyl-4-yl)-amide,

[0647]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid (2′-methanesulfonyl-biphenyl-4-yl)-amide,

[0648]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenyl]-amide,

[0649]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (4-morpholin-4-yl-phenyl)-amide,

[0650]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(1H-imidazol-4-yl)-phenyl]-amide,

[0651]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (4-piperidin-1-yl-phenyl)-amide,

[0652]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-indazole-5-carboxylicacid methyl ester,

[0653]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester,

[0654]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid,

[0655]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester,

[0656]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(cyanamide-1-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,

[0657]1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-azetidine-3-carboxylicacid,

[0658]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(3-oxo-morpholin-4-yl)-phenyl]-amide,

[0659]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(4-oxo-4H-pyridin-1-yl)-phenyl]-amide,

[0660]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(4-oxo-4H-pyridin-1-yl)-phenyl]-amide,

[0661]1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-methoxy-ethyl ester,

[0662]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-hydroxy-ethyl ester, or

[0663]1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-([1,4]oxazepane-4-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide.

[0664] Salts of compounds of the formula I can be obtained by customarymethods known to those skilled in the art, for example by combining acompound of the formula I with an inorganic or organic acid or base in asolvent or dispersant, or from other salts by cation exchange or anionexchange. The present invention also includes all salts of the compoundsof the formula I which, because of low physiologically tolerability, arenot directly suitable for use in pharmaceuticals but are suitable, forexample, as intermediates for carrying out further chemicalmodifications of the compounds of the formula I or as starting materialsfor the preparation of physiologically tolerable salts.

[0665] The present invention furthermore includes all solvates ofcompounds of the formula I, for example hydrates or adducts withalcohols.

[0666] The invention also includes derivatives and modifications of thecompounds of the formula I, for example prodrugs, protected forms andother physiologically tolerable derivatives, as well as activemetabolites of the compounds of the formula I. The invention relates inparticular to prodrugs and protected forms of the compounds of theformula I, which can be converted into compounds of the formula I underphysiological conditions. Suitable prodrugs for the compounds of theformula I, i. e. chemically modified derivatives of the compounds of theformula I having properties which are improved in a desired manner, forexample with respect to solubility, bioavailability or duration ofaction, are known to those skilled in the art. More detailed informationrelating to prodrugs is found in standard literature like, for example,Design of Prodrugs, H. Bundgaard (ed.), Elsevier, 1985; Fleisher et al.,Advanced Drug Delivery Reviews 19 (1996) 115-130; or H. Bundgaard, Drugsof the Future 16 (1991) 443 which are all incorporated herein byreference. Suitable prodrugs for the compounds of the formula I areespecially acyl prodrugs and carbamate prodrugs of acylatablenitrogen-containing groups such as amino groups and the guanidino groupand also ester prodrugs and amide prodrugs of carboxylic acid groupswhich may be present in compounds of the formula I. In the acyl prodrugsand carbamate prodrugs one or more, for example one or two, hydrogens onnitrogen atoms in such groups are replaced with an acyl group or acarbamate, preferably a —(C₁-C₆)-alkyloxycarbonyl group. Suitable acylgroups and carbamate groups for acyl prodrugs and carbamate prodrugsare, for example, the groups R^(p1)—CO— and R^(p2)O—CO—, in which R^(p1)is hydrogen, (C₁-C₈)-alkyl, (C₃-C₈)-cycloalkyl,(C₃-C₈)-cycloalkyl-(C₁-C₄)-alkyl-, (C₆-CI₄)-aryl, Het-,(C₆-C₁₄)-aryl-(C₁-C₄)-alkyl- or Het-(C₁-C₄)-alkyl- and in which R^(p2)has the meanings indicated for R^(p1) with the exception of hydrogen.

[0667] Especially preferred compounds of the formula I are those whereintwo or more residues are defined as indicated before for preferredcompounds of the formula I, or residues can have one or some of thespecific denotations of the residues given in their general definitionsor in the definitions of preferred compounds before. All possiblecombinations of definitions given for preferred definitions and ofspecific denotations of residues explicitly are a subject of the presentinvention.

[0668] Also with respect to all preferred compounds of the formula I alltheir stereoisomeric forms and mixtures thereof in any ratio and theirphysiologically acceptable salts explicitly are a subject of the presentinvention, as well as are their prodrugs. Similarly, also in allpreferred compounds of the formula I, all residues that are present morethan one time in the molecule are independent of each other and can beidentical or different.

[0669] The compounds of the formula I can be prepared by utilisingprocedures and techniques, which per se are well known and appreciatedby one of ordinary skill in the art. Starting materials or buildingblocks for use in the general synthetic procedures that can be appliedin the preparation of the compounds of formula I are readily availableto one of ordinary skill in the art. In many cases they are commerciallyavailable or have been described in the literature. Otherwise they canbe prepared from readily available precursor compounds analogously toprocedures described in the literature, or by procedures or analogouslyto procedures described in this application.

[0670] In general, compounds of the formula I can be prepared, forexample in the course of a convergent synthesis, by linking two or morefragments which can be derived retrosynthetically from the formula I.More specifically, suitably substituted starting Indazole derivativesare employed as building blocks in the preparation of the compounds offormula I. If not commercially available, such Indazole derivatives canbe prepared according to the well-known standard procedures for theformation of the Indazole ring system. By choosing suitable precursormolecules, these pyrazole syntheses allow the introduction of a varietyof substituents into the various positions of the pyrazole system, whichcan be chemically modified in order to finally arrive at the molecule ofthe formula I having the desired substituent pattern. As one of thecomprehensive reviews in which numerous details and literaturereferences on the chemistry of indazole and on synthetic procedures fortheir preparation can be found, J. Eiguero in “ComprehensiveHeterocyclic Chemistry II”; Eds. A. Katritzky, Ch. Rees, E. Scriven;Elsevier 1996, Vol. 3; W. Stadlbauer in Houben-Weyl, “Methoden derOrganischen Chemie” (Methods of Organic Chemistry), Georg Thieme Verlag,Stuttgart, Germany 1994, Vol. E8b Hetarene.

[0671] If starting indazole derivatives are not commercially availableand have to be synthesized this can be done, for example, according tothe well-known indazole syntheses mentioned above. In the followingprocedures of particular interest for the embodiment of this inventionare listed and referenced briefly, however, they are standard procedurescomprehensively discussed in the literature, and are well known to oneskilled in the art. Although not always shown explicitly, in certaincases positional isomers will occur during the synthesis of the belowmentioned reactions. Nevertheless such mixtures of positional isomers,can be separated by modern separation techniques like, for example,preparative HPLC.

[0672] 1) M. Sisti et al. J. Heterocyclic. Chem. (1989) 26, 531.

[0673] 2) a) R. M. Scarborough et al., J. Med. Chem. (1997) 40, 2843.

[0674] b) C. S. Harms et al., J. Med. Chem. (1997) 40, 2843.

[0675] c) A. E. Arfsten et al., J. Med. Chem. (1997) 40, 4308.

[0676] 3) a) T. Yoshida et al., Heterocycles (1996) 43, 2701.

[0677] 4) a) J. J. Song et al., Tetrahedron Lett. (2001) 42, 2937.

[0678] b) J. J. Song et al., Org. Lett. (2000) 2, 519.

[0679] 5) M. M. Abdel-Khalik et al., Synthesis (2000) 8, 1166.

[0680] 6) S. Caron et al., Synthesis (1999) 4, 588.

[0681] 7) S. F. Vasilevsky et al., Mendeleev Commun. (1998) 4, 149.

[0682] 8) a) T. Yoshida et al., Heterocycles (1996) 43, 2701.

[0683] b) D. A. Nugiel et al., J. Org. Chem. (1997) 62, 5627.

[0684] 9) a) F. Halley et al., Synth. Commun. (1997) 27, 1199.

[0685] b) A. Walser et al., J. Heterocycl. Chem. (1991) 28, 1121.

[0686] c) G. M. Shutzke et al., J. Heterocycl. Chem. (1997) 34, 1121.

[0687] 10) K. Tumbull et al., Synth. Commun. (1996) 26, 2757.

[0688] 11) a) Z. Zong et al., J. Chem. Soc. Perkin Trans 1 (1993) 1279.

[0689] b) P. G. Baraldi et al., Synthesis (1997) 1140.

[0690] 12) R. L. Swett et al., J. Heterocycl. Chem. (1975) 12, 517.

[0691] 13) Y. Tominaga et al., Tetrahedron Lett. (1995) 47, 8641.

[0692] 14) V. K. Ahluwalia et a]., Synth. Commun. (1996) 26, 1341.

[0693] 15) F. von Meyenburg et al., Chem. Ber. (1891) 24, 2370.

[0694] 16) B. N. Bradbury et al., J. Chem. Soc. Perkin Trans 1 (1975)31.

[0695] 17) B. Gonzalez et al., J. Chem. Res. Miniprint (1985) 1128.

[0696] 18) a) A. R. Frasca et al., Tetrahedron Lett. (1962) 1115.

[0697] b) A. R. Frasca et al.,Can. J. Chem. (1967) 45, 697.

[0698] 19) K. Tumbull et al., J. Heterocycl. Chem. (1988) 25, 1817.

[0699] 20) C. Tavani et al., Tetrahedron (I1994) 50, 3529.

[0700] 21) a) I. Fujiwara et al., Chem. Pharm Bull. (1995) 43, 1912.

[0701] b) G. C. Rigdon et al., J. Med. Chem. (1996) 39, 4692.

[0702] Furthermore for those who are skilled in the art it will cause nodifficulty to adopt and modify certain procedures describing thesynthesis and derivatisation of pyrazoles to indazoles. These proceduresare, for example, described by J. Eiguero in “Comprehensive HeterocyclicChemistry II”; Eds. A. Katritzky, Ch. Rees, E. Scriven; Elsevier 1996,Vol. 3; K. Kirschke in Houben-Weyl, “Methoden der Organischen Chemie”(Methods of Organic Chemistry), Georg Thieme Verlag, Stuttgart, Germany1994, Vol. E8b Hetarene; T. Nagai et al. Org. Prep. Proced. Int. (1993),25, 403; M. Elnagdi et al., Heterocycles (1985) 23, 3121; K. Makino etal., J. Heterocycl. Chem. (1998) 35, 489; K. Makino et al., J.Heteterocycl. Chem. (1999) 36, 321.

[0703] In particular applying and modiflying procedures for thesynthesis of pyrazole derivatives listed and briefly referenced below,can open-up access to valuable intermediates for the synthesis ofcompounds of the formula I.

[0704] 1) a) N. Kudo et al. Chem. Pharm. Bull. (1999) 47, 857.

[0705] b) M. Dewar et al. J. Chem. Soc. (1945) 114.

[0706] c) L. J. Smith, J. Am. Chem. Soc. (1949) 71, 2671.

[0707] d) J. Zhang,et al., Bioorg. Med. Chem. Lett. (2000) 10, 2575.

[0708] 2) a) A. Padwa, J. Heterocycl. Chem. (1987) 24, 1225.

[0709] b) A. W. Erian et al.; Synth Commun. (1999) 29, 1527.

[0710] 3) N. K. Markova et al., Zh. Org. Khim. (1983) 19, 2281.

[0711] 4) P. Bravo et al., Tetrahedron (1994) 50, 8827.

[0712] 5) a) M. A. Martins et al., Synthesis (1995) 12, 1491.

[0713] b) M. A. Martins et al., J. Heterocycl. Chem. (1999) 36, 217.

[0714] 6) R. G. Jones et al., J. Org. Chem. (1955) 20, 1342.

[0715] 7) W. T. Ashton et al., J. Heterocycl. Chem. (1993) 30, 307.

[0716] 8) a) K. I. Bookernilburn, Synlett, (1992) 327.

[0717] b) G. Heinisch et al., J. Chem. Soc. Perkin. Trans 1 (1990) 1829.

[0718] c) K. Tumbull et al., Org. Prep. Proced. Int. (2000) 32, 593

[0719] 9) F. Farina et al., Heterocycles (1989) 29, 967.

[0720] 10) T. Haque et al., J. Med. Chem. (2002) 4669.

[0721] 11) H. V. Patel, Synth. Commun. (1991) 21, 1583.

[0722] 12) F. Farina et al., Heterocycles (1989) 29, 967.

[0723] 13) R. Huisgen et al., J. Am. Chem. Soc. (1979) 101, 3647.

[0724] 14) W. Sucrow et al., Angew. Chem., Int. Ed. (1975) 14, 560.

[0725] 15) C. Baldoli et al., J. Heterocycl. Chem. (1989), 26, 241.

[0726] 16) G. M. Pilling et al., Tetrahedron Lett. (1988) 29, 1341.

[0727] 17) D. Sauer et al., J. Org. Chem. (1990) 55, 5535.

[0728] 18) K. Washizuka et al., Tetrahedron Lett. (1999) 40, 8849.

[0729] 19) F. Foti et al., Tetrahedron Lett. (1999) 40, 2605.

[0730] Further, in order to obtain the desired substituents at theindazole ring system in the formula I, the functional groups introducedinto the ring system during the indazole synthesis can be chemicallymodified. Especially the groups present in the indazole ring system canbe modified by a variety of reactions and thus the desired residues R³can be obtained. For example, an indazole carrying hydrogen in the3-position can also be obtained by saponification and subsequentdecarboxylation of indazole carrying an ester group in the respectiveposition. Alkyl- or hydroxymethyl groups as well as formyl groupsattached to the indazole core can be transformed to a variety offunctional groups, for example, to the corresponding carboxylic acid orcarboxylic ester by many oxidative reactions well known to those skilledin the art. Moreover a nitrile group attached to the indazole ring can,for example, easily be converted into the desired acid under acidic orbasic conditions. In addition, carboxylic acid groups and acetic acidgroups in the 3-position can be converted into their homologues by usualreactions for chain elongation of carboxylic acids. Halogen atoms can beintroduced into the 3-position for example according to procedures likethe following described in the literature. For the fluorinationN-fluoro-2,4,6-trimethylpyridinium triflate is a suitable reagent (T.Umemoto, S. Fukami, G. Tomizawa, K. Harasawa, K. Kawada, K. Tomita, J.Am. Chem. Soc. (1990) 112, 8563 see also K. Manko et al., J. FluorineChem. (1988) 39, 435; R. Storer et al. Nucleosides Nucleotides (1999)18; 203) however, other fluorinating reagents may also be employed whereappropriate. The chlorination, brominnation, or iodination of indazolescan be accomplished by the reaction with elemental halogens or by theuse of NCS, NBS or NIS and many other reagents well known to thoseskilled in the art. In addition suitable procedures are, in analogy tothe related pyrazoles, for example reported by M. Rodriguez-Franco etal., Tetrahedron Lett. (2001) 42, 863; J. Pawlas et al., J. Org. Chem.(2000) 65, 9001; Y. Huang et al., Org Lett (2000) 2, 2833; W. Holzer etal., J. Heterocycl. Chem. (1995) 32, 1351; N. Kudo et al., Chem. Pharm.Bull. (1999) 47, 857; G. Auzzi et al., Farmaco, Ed Sci (1979) 34, 743;K. Morimoto et al., J. Heterocycl. Chem. (1997) 34, 537; D. Jeon et al.,Synth. Commun. (1998) 28, 2159.

[0731] Depending on the reaction conditions, reagent, stochiometry andsubstitution pattern the halogen is introduced in the 3-position. Byselective halogen/metal exchange or metalation by selectivehydrogen/metal exchange and subsequent reaction with a wide range ofelectrophiles various substituents can be introduced at the heterocyclicnucleus. (W. M. Welch et al., Synthesis (1992) 937; M. R. Grimmett,Heterocycles (1994) 37, 2087; V. D. Gardner et al., J. Heterocycl. Chem.(1984) 21, 121; D. Butler et al., J. Org. Chem. (1971) 36, 2542).Halogens or hydroxy groups (via their triflates or nonaflates)—orprimary amines (via their diazonium salts) present in the indazolestructure—can be converted directly, or after interconversion to thecorresponding stannane, or boronic acid,into a variety of otherfunctional groups like for example —CN, —CF₃, —C₂F₅, ethers, acids,amides, amines, alkyl- or aryl-groups mediated by means of transitionmetals, namely palladium or nickel catalysts or copper salts andreagents for example referred to below (F. Diederich, P. Stang,Metal-catalyzed Cross-coupling Reactions, Wiley-VCH, 1998; or M. Beller,C. Bolm, Transition Metals for Organic Synthesis, Wiley-VCH, 1998; J.Tsuji, Palladium Reagents and Catalysts, Wiley, 1996; J. Hartwig, Angew.Chem. (1998) 110, 2154; B. Yang, S. Buchwald, J. Organomet. Chem. (1999)576, 125; T. Sakamoto, K. Ohsawa, J. Chem. Soc. Perkin Trans 1 (1999)2323; D. Nichols, S. Frescas, D. Marona-Lewicka, X. Huang, B. Roth, G.Gudelsky, J. Nash, J. Med. Chem. (1994) 37, 4347; P. Lam, C. Clark, S.Saubern, J. Adams, M. Winters, D. Chan, A. Combs, Tetrahedron Lett.(1998) 39,2941; D. Chan, K. Monaco, R. Wang, M. Winters, TetrahedronLett. (1998) 39, 2933; V. Farina, V. Krishnamurthy, W. Scott, The StilleReaction, Wiley, 1994; F. Qing et al. J. Chem. Soc. Perkin Trans. I(1997) 3053; S. Buchwald et al. J. Am. Chem Soc. (2001) 123, 7727; S.Kang et al. Synlett (2002) 3, 427; S. Buchwald et al. Organic Lett.(2002) 4, 581; T. Fuchikami et al. Tetrahedron Lett. (1991) 32, 91; Q.Chen et al. Tetrahedron Lett. (1991) 32, 7689).

[0732] For example, nitro groups can be reduced to amino groups by meansof various reducing agents, such as sulfides, dithionites, complexhydrides or by catalytic hydrogenation. A reduction of a nitro group mayalso be carried out at a later stage of the synthesis of a compound ofthe formula I, and a reduction of a nitro group to an amino group mayalso occur simultaneously with a reaction performed on anotherfunctional group, for example when reacting a group like a cyano groupwith hydrogen sulfide or when hydrogenating a group. In order tointroduce the residues R³, amino groups can then be modified accordingto standard procedures for alkylation, for example by reaction with(substituted) alkyl halogenides or by reductive amination of carbonylcompounds, according to standard procedures for acylation, for exampleby reaction with activated carboxylic acid derivatives such as acidchlorides, anhydrides, activated esters or others or by reaction withcarboxylic acids in the presence of an activating agent, or according tostandard procedures for sulfonylation, for example by reaction withsulfonyl chlorides.

[0733] Ester groups present in the indazole nucleus can be hydrolyzed tothe corresponding carboxylic acids, which after activation can then bereacted with amines or alcohols under standard conditions to give amidesor alcohols, respectively. Ester groups present in the indazole nucleuscan be converted to other esters by transesterification. Carboxylicacids attached to a suitable indazole nucleus can also be alkylated togive esters. Ether groups present at the indazole nucleus, for examplebenzyloxy groups or other easily cleavable ether groups, can be cleavedto give hydroxy groups which then can be reacted with a variety ofagents, for example etherification agents or activating agents allowingreplacement of the hydroxy group by other groups. Sulfur-containinggroups can be reacted analogously.

[0734] During the course of the synthesis in order to modify the groupsR¹³⁶ or R^(8′) attached to the indazole ring system by application ofparallel synthesis methodology, a variety of reactions can be extremelyuseful, including, for example, palladium, nickel or copper catalysis.Such reactions are described for example in F. Diederich, P. Stang,Metal-catalyzed Cross-coupling Reactions, Wiley-VCH (1998); or M.Beller, C. Bolm, Transition Metals for Organic Synthesis, Wiley-VCH(1998); J. Tsuji, Palladium Reagents and Catalysts, Wiley (1996); J.Hartwig, Angew. Chem. (1998) 110, 2154; B. Yang, S. Buchwald, J.Organomet. Chem. (1999) 576, 125; P. Lam, C. Clark, S. Saubern, J.Adams, M. Winters, D. Chan, A. Combs, Tetrahedron Lett. (1998) 39, 2941;D. Chan, K. Monaco, R. Wang, M. Winters, Tetrahedron Lett. (1998) 39,2933; J. Wolfe, H. Tomori, J. Sadight, J. Yin, S. Buchwald, J. Org.Chem. (2000) 65, 1158; V. Farina, V. Krishnamurthy, W. Scott, The StilleReaction, Wiley, (1994); S. Buchwald et al., J. Am. Chem. Soc. (2001)123, 7727; S. Kang et al., Synlett (2002) 3, 427; S. Buchwald et al.,Org. Lett. (2002) 4, 581.

[0735] The previously-mentioned reactions for the conversion offunctional groups are furthermore, in general, extensively described intextbooks of organic chemistry like M. Smith, J. March, March's AdvancedOrganic Chemistry, Wiley-VCH, 2001 and in treatises like Houben-Weyl,“Methoden der Organischen Chemie” (Methods of Organic Chemistry), GeorgThieme Verlag, Stuttgart, Germany, or “Organic Reactions”, John Wiley &Sons, New York, or R. C. Larock, “Comprehensive OrganicTransformations”, Wiley-VCH, 2^(nd) ed (1999), B. Trost, I. Fleming(eds.) Comprehensive Organic Synthesis, Pergamon, 1991; A. Katritzky, C.Rees, E. Scriven Comprehensive Heterocyclic Chemistry II, ElsevierScience, 1996) in which details on the reactions and primary sourceliterature can be found. Due to the fact that in the present case thefunctional groups are attached to an indazole ring it may in certaincases become necessary to specifically adapt reaction conditions or tochoose specific reagents from a variety of reagents that can inprinciple be employed into a conversion reaction, or otherwise to takespecific measures for achieving a desired conversion, for example to useprotection group techniques. However, finding out suitable reactionvariants and reaction conditions in such cases does not cause anyproblems for one skilled in the art.

[0736] The structural elements present in the residues attached at the1-position or 2-position of the indazole ring in the compounds of theformula I and in the COR^(8′) group present in the 3-position of theindazole ring can be introduced into the starting indazole derivativeobtainable as outlined above by consecutive reaction steps usingsynthesis methodologies like those outlines below using procedures whichper se are well known to one skilled in the art. The sequence describedbelow can be completely transferred to compounds of the formula Ib asoutlined.

[0737] The residues R^(8′) that can be introduced in formula 2, forexample, by condensing a corresponding carboxylic acid of the formula 2with a compound of the formula HR^(8′), i.e. with an amine of theformula HN(R^(1′))R²′—V-G-M to give a compound of the formula 3. Thecompound of the formula 3 thus obtained can already contain the desiredfinal groups, i.e. the groups R^(8′) and R¹³⁶ can be the groups—N(R¹)—R²—V-G-M and R⁰-Q- as defined in the formula I, or optionally inthe compound of the formula 3 thus obtained subsequently the residue orthe residues R^(8′) and the residue R¹³⁶ are introduced or convertedinto the residues —N(R¹)R²—V-G-M and R⁰-Q-, respectively, to give thedesired compound of the formula I, wherein J₁ is N and J₂ is N—Q—R⁰.

[0738] Thus, the residues R^(8′) and the residues R^(1′) and R²′—V-G-Mcontained therein can have the denotations of R¹ and R²—V-G-M,respectively, given above or in addition in the residues R^(1′) andR²′—V-G-M functional groups can also be present in the form of groupsthat can subsequently be transformed into the final groups R¹ andR²—V-G-M, i.e. functional groups can be present in the form of precursorgroups or of derivatives, for example in protected form. In the courseof the preparation of the compounds of the formula I it can generally beadvantageous or necessary to introduce functional groups which reduce orprevent undesired reactions or side reactions in the respectivesynthesis step, in the form of precursor groups which are laterconverted into the desired functional groups, or to temporarily blockfunctional groups by a protective group strategy suited to the synthesisproblem. Such strategies are well known to those skilled in the art(see, for example, Greene and Wuts, Protective Groups in OrganicSynthesis, Wiley, 1991, or P. Kocienski, Protecting Groups, Thieme1994). As examples of precursor groups nitro groups and cyano groups maybe mentioned which can in a later step be transformed into carboxylicacid derivatives or by reduction into aminomethyl groups, or nitrogroups which may be transformed by reduction, for example catalytichydrogenation into amino groups by reduction. Protective groups can alsohave the meaning of a solid phase, and cleavage from the solid phasestands for the removal of the protective group. The use of suchtechniques is known to those skilled in the art (Burgess K (Ed.) SolidPhase Organic Synthesis, New York, Wiley, 2000). For example, a phenolichydroxy group can be attached to a trityl-polystyrene resin, whichserves as a protecting group, and the molecule is cleaved from thisresin by treatment with TFA at a later stage of the synthesis.

[0739] The residue R¹³⁶ in the compounds of the formulae 2 and 3 candenote the group -Q-R⁰ as defined above which finally is to be presentin the desired target molecule of the formula I, or it can denote agroup which can subsequently be transformed into the group -Q-R⁰, forexample a precursor group or a derivative of the group -Q-R⁰ in whichfunctional groups are present in protected form, or R¹³⁶ can denotehydrogen or a protective group for the nitrogen atom of the indazolering. Similarly, the residue R³ in the formulae 2 and 3 have thecorresponding definitions of R³ in formula I as defined above, however,for the synthesis of the compounds of the formula I these residues, too,can in principle be present at the stage of the condensation of acompound of the formula 2 with a compound of the formula HR^(8′) givinga compound of the formula 3 in the form of precursor groups or inprotected form.

[0740] The residues R¹³⁵ in the compounds of the formula 2 which can beidentical or different, can be, for example, hydroxy or (C₁-C₄)-alkoxy,i.e., the groups COR¹³⁵ present in the compounds of the formula 2 canbe, for example, the free carboxylic acids or esters thereof like alkylesters as can be the groups COR^(8′) in the compounds of the formula I.The groups COR¹³⁵ can also be any other activated derivative of acarboxylic acid which allows amide formation, ester formation orthioester formation with a compound of the formula HRR^(8′). The groupCOR¹³⁵ can be, for example, an acid chloride, an activated ester like asubstituted phenyl ester or an N-hydroxysuccinimide or ahydroxybenzotriazole ester, an azolide like an imidazolide, an azide ora mixed anhydride, for example a mixed anhydride with a carbonic acidester or with a sulfonic acid, which derivatives can all be preparedfrom the carboxylic acid by standard procedures and can be reacted withan amine, an alcohol or a mercaptan of the formula HR^(8′) understandard conditions. A carboxylic acid group COOH representing COR¹³⁵ ina compound of the formula 2 can be obtained, for example, from an estergroup introduced into the indazole system during a indazole synthesis bystandard hydrolysis procedures. It can also be obtained, for example, byhydrolysis of a nitrile group introduced into the indazole system duringan indazole sysnthesis.

[0741] Compounds of the formula I in which a group COR^(8′) is an estergroup can also be prepared from compounds of the formula 2 in whichCOR¹³⁵ is a carboxylic acid group by common esterification reactionslike, for example, reacting the acid with an alcohol under acidcatalysis, or alkylation of a salt of the carboxylic acid with anelectrophile like an alkyl halogenide, or by transesterification fromanother ester. Compounds of the formula I in which a group COR^(8′) isan amide group can be prepared from amines and compounds of the formula2 in which COR¹³⁵ is a carboxylic acid group or an ester thereof bycommon amination reactions. Especially for the preparation of amides thecompounds of the formula 2 in which COR¹³⁵ is a carboxylic acid groupcan be condensed under standard conditions with compounds of the formulaHR^(8′) which are amines by means of common coupling reagents used inpeptide synthesis. Such coupling reagents are, for example,carbodiimides like dicyclohexylcarbodiimide (DCC) ordiisopropylcarbodiimide, carbonyldiazoles like carbonyldiimidazole (CDI)and similar reagents, propylphosphonic anhydride,O-((cyano-(ethoxycarbonyl)-methylene)amino)-N,N,N′,N′-tetramethyluroniumtetrafluoroborate (TOTU), diethylphosphoryl cyanide (DEPC) orbis-(2-oxo-3-oxazolidinyl)-phosphoryl chloride (BOP-Cl) and many others.

[0742] If the residue -Q-R⁰ present in an indazole of the formula I orthe residue R¹³⁶ present in an indazole of the formula 2, or a residuein which functional groups within the residue -Q-R⁰ or R¹³⁶ are presentin protected form or in the form of a precursor group, have not alreadybeen introduced during a preceding step, for example during a synthesisof the indazole nucleus, these residues can, for example, be introducedinto the 1-position of the indazole system by conventional literatureprocedures well known to one skilled in the art for N-alkylation,reductive amination, N-arylation, N-acylation or N-sulfonylation of ringnitrogen atoms of heterocycles. The starting indazole derivative that isto be employed in such a reaction carries hydrogen in the 1-position.N-Alkylation of a ring nitrogen atom can, for example, be performedunder standard conditions, preferably in the presence of a base likeK₂CO₃, Cs₂CO₃, NaH or KO^(t)Bu, using an alkylating compound of theformula LG-Q-R⁰ or of the formula R¹³⁶-LG, wherein the atom in the groupQ or in the group R¹³⁶ bonded to the group LG in this case is analiphatic carbon atom of an alkyl moiety and LG is a leaving group, forexample halogen like chlorine, bromine or iodine, or a sulfonyloxy grouplike tosyloxy, mesyloxy or trifluormethylsulfonyloxy. LG may, forexample, also be a hydroxy group which, in order to achieve thealkylation reaction, is activated in a well-known Mitsunobu reaction bya conventional activating agent. The regioselectivity of theN-alkylation can be controlled by the choice of the base, solvent andreaction conditions. Nevertheless mixtures of positional isomers, can beseparated by modern separation techniques like, for example, flashchromatography, crystallisation or preparative HPLC.

[0743] The sequence described above for compounds of the formula I,wherein J₁ is N and J₂ is N—Q—R⁰, can be completely transferred tocompounds of the formula I, wherein J₂ is N and J₁ is N—Q—R⁰, asoutlined by the scheme below.

[0744] For the preparation of compounds in which A is a direct linkageand an aromatic group is directly bonded to the 1-position or 2-positionof the indazole system, conventional arylation procedures can be used.For example aryl fluorides like alkyl fluorobenzoates or 4-fluorophenylnitriles can be employed as arylating agents. Such processes aredescribed, for example, by K. Cooper et al., J.Med.Chem. (1992), 35,3115; M. Artico et al., Eur.J.Med.Chem.Chim.Ther. (1992) 27, 219; X.-J.Wang et al., Tetrahedron Letters (2000) 41, 5321; M. L. Cerrada et al.,Synth. Commun. (1993) 23, 1947. Alternatively a wide variety ofsubstituted aryl iodides, aryl bromides or aryl triflates can serve asarylating agents at the 1-position or 2-position of the heterocyclicnitrogen in a copper salt or palladium mediated reaction according forexample to P. Cozzi et al. Farmaco (1987) 42, 205; P. Unangst, D.Connor, R. Stabler, R. Weikert, J. Heterocycl. Chem. (1987) 24, 811; G.Tokmakov, I. Grandberg, Tetrahedron (1995) 51, 2091; D. Old, M. Harris,S. Buchwald, Org. Lett. (2000) 2, 1403, G. Mann, J. Hartwig, M. Driver,C. Femandez-Rivas, J. Am. Chem. Soc. (1998) 120, 827; J. Hartwig, M.Kawatsura, S. Hauk, K. Shaughnessy, L. J. Org. Chem. (1999) 64, 5575; S.Buchwald et al., J. Am. Chem. Soc. (2001) 123, 7727. Moreover sucharylations can also be accomplished by reaction of a wide range ofsubstituted aryl boronic acids as demonstrated for example by P. Lam etal., Tetrahedron Lett. (1998) 39, 2941; V. Collot et al., TetrahedronLett. (2000) 41, 9053; P. Lam et al., Tetrahedron Lett. (2001) 42, 3415;

[0745] Preferred methods include, but are not limited to those describedin the examples.

[0746] The compounds of the present invention are serine proteaseinhibitors, which inhibit the activity of the blood coagulation enzymefactors Xa and/or factor VIIa. In particular, they are highly activeinhibitors of factor Xa. They are specific serine protease inhibitorsinasmuch as they do not substantially inhibit the activity of otherproteases whose inhibition is not desired. The activity of the compoundsof the formula I can be determined, for example, in the assays describedbelow or in other assays known to those skilled in the art. With respectto factor Xa inhibition, a preferred embodiment of the inventioncomprises compounds which have a Ki<1 mM for factor Xa inhibition asdetermined in the assay described below, with or without concomitantfactor VIIa inhibition, and which preferably do not substantiallyinhibit the activity of other proteases involved in coagulation andfibrinolysis whose inhibition is not desired (using the sameconcentration of the inhibitor). The compounds of the invention inhibitfactor Xa catalytic activity either directly, within the prothrombinasecomplex or as a soluble subunit, or indirectly, by inhibiting theassembly of factor Xa into the prothrombinase complex.

[0747] As inhibitors of factor Xa and/or factor VIIa the compounds ofthe formula I and their physiologically tolerable salts and theirprodrugs are generally suitable for the therapy and prophylaxis ofconditions in which the activity of factor Xa and/or factor VJIa plays arole or has an undesired extent, or which can favorably be influenced byinhibiting factor Xa and/or factor VIIa or decreasing their activities,or for the prevention, alleviation or cure of which an inhibition offactor Xa and/or factor VIIa or a decrease in their activity is desiredby the physician. As inhibition of factor Xa and/or factor VIIainfluences blood coagulation and fibrinolysis, the compounds of theformula I and their physiologically tolerable salts and their prodrugsare generally suitable for reducing blood clotting, or for the therapyand prophylaxis of conditions in which the activity of the bloodcoagulation system plays a role or has an undesired extent, or which canfavorably be influenced by reducing blood clotting, or for theprevention, alleviation or cure of which a decreased activity of theblood coagulation system is desired by the physician. A specific subjectof the present invention thus are the reduction or inhibition ofunwanted blood clotting, in particular in an individual, byadministering an effective amount of a compound I or a physiologicallytolerable salt or a prodrug thereof, as well as pharmaceuticalpreparations therefore.

[0748] The present invention also relates to the compounds of theformula I and/or their physiologically tolerable salts and/or theirprodrugs for use as pharmaceuticals (or medicaments), to the use of thecompounds of the formula I and/or their physiologically tolerable saltsand/or their prodrugs for the production of pharmaceuticals forinhibition of factor Xa and/or factor VIa or for influencing bloodcoagulation, inflammatory response or fibrinolysis or for the therapy orprophylaxis of the diseases mentioned above or below, for example forthe production of pharmaceuticals for the therapy and prophylaxis ofcardiovascular disorders, thromboembolic diseases or restenoses. Theinvention also relates to the use of the compounds of the formula Iand/or their physiologically tolerable salts and/or their prodrugs forthe inhibition of factor Xa and/or factor VIIa or for influencing bloodcoagulation or fibrinolysis or for the therapy or prophylaxis of thediseases mentioned above or below, for example for use in the therapyand prophylaxis of cardiovascular disorders, thromboembolic diseases orrestenoses, and to methods of treatment aiming at such purposesincluding methods for said therapies and prophylaxis. The presentinvention also relates to pharmaceutical preparations (or pharmaceuticalcompositions) which contain an effective amount of at least one compoundof the formula I and/or its physiologically tolerable salts and/or itsprodrugs in addition to a customary pharmaceutically acceptable carrier,i.e. one or more pharmaceutically acceptable carrier substances orexcipients and/or auxiliary substances or additives.

[0749] The invention also relates to the treatment of disease statessuch as abnormal thrombus formation, acute myocardial infarction,unstable angina, thromboembolism, acute vessel closure associated withthrombolytic therapy or percutaneous transluminal coronary angioplasty(PTCA), transient ischemic attacks, stroke, intermittent claudication orbypass grafting of the coronary or peripheral arteries, vessel luminalnarrowing, restenosis post coronary or venous angioplasty, maintenanceof vascular access patency in long-term hemodialysis patients,pathologic thrombus formation occurring in the veins of the lowerextremities following abdominal, knee or hip surgery, pathologicthrombus formation occurring in the veins of the lower extremitiesfollowing abdominal, knee and hip surgery, a risk of pulmonarythromboembolism, or disseminated systemic intravascular coagulatopathyoccurring in vascular systems during septic shock, certain viralinfections or cancer.

[0750] The compounds of the present invention can also be used to reducean inflammatory response. Examples of specific disorders for thetreatment or prophylaxis of which the compounds of the formula I can beused are coronary heart disease, myocardial infarction, angina pectoris,vascular restenosis, for example restenosis following angioplasty likePTCA, adult respiratory distress syndrome, multi-organ failure anddisseminated intravascular clotting disorder. Examples of relatedcomplications associated with surgery are thromboses like deep vein andproximal vein thrombosis, which can occur following surgery.

[0751] The compounds of the formula I and their physiologicallytolerable salts and their prodrugs can be administered to animals,preferably to mammals, and in particular to humans as pharmaceuticalsfor therapy or prophylaxis. They can be administered on their own, or inmixtures with one another or in the form of pharmaceutical preparations,which permit enteral or parenteral administration.

[0752] The pharmaceuticals can be administered orally, for example inthe form of pills, tablets, lacquered tablets, coated tablets, granules,hard and soft gelatin capsules, solutions, syrups, emulsions,suspensions or aerosol mixtures. Administration, however, can also becarried out rectally, for example in the form of suppositories, orparenterally, for example intravenously, intramuscularly orsubcutaneously, in the form of injection solutions or infusionsolutions, microcapsules, implants or rods, or percutaneously ortopically, for example in the form of ointments, solutions or tinctures,or in other ways, for example in the form of aerosols or nasal sprays.

[0753] The pharmaceutical preparations according to the invention areprepared in a manner known per se and familiar to one skilled in theart, pharmaceutically acceptable inert inorganic and/or organic carriersbeing used in addition to the compound(s) of the formula I and/or its(their) physiologically tolerable salts and/or its (their) prodrugs. Forthe production of pills, tablets, coated tablets and hard gelatincapsules it is possible to use, for example, lactose, cornstarch orderivatives thereof, talc, stearic acid or its salts, etc. Carriers forsoft gelatin capsules and suppositories are, for example, fats, waxes,semisolid and liquid polyols, natural or hardened oils, etc. Suitablecarriers for the production of solutions, for example injectionsolutions, or of emulsions or syrups are, for example, water, saline,alcohols, glycerol, polyols, sucrose, invert sugar, glucose, vegetableoils, etc. Suitable carriers for microcapsules, implants or rods are,for example, copolymers of glycolic acid and lactic acid. Thepharmaceutical preparations normally contain about 0.5% to 90% by weightof the compounds of the formula I and/or their physiologically tolerablesalts and/or their prodrugs. The amount of the active ingredient of theformula I and/or its physiologically tolerable salts and/or its prodrugsin the pharmaceutical preparations normally is from about 0.5 mg toabout 1000 mg, preferably from about 1 mg to about 500 mg.

[0754] In addition to the active ingredients of the formula I and/ortheir physiologically acceptable salts and/or prodrugs and to carriersubstances, the pharmaceutical preparations can contain additives suchas, for example, fillers, disintegrants, binders, lubricants, wettingagents, stabilizers, emulsifiers, preservatives, sweeteners, colorants,flavorings, aromatizers, thickeners, diluents, buffer substances,solvents, solubilizers, agents for achieving a depot effect, salts foraltering the osmotic pressure, coating agents or antioxidants. They canalso contain two or more compounds of the formula I, and/or theirphysiologically tolerable salts and/or their prodrugs. In case apharmaceutical preparation contains two or more compounds of the formulaI, the selection of the individual compounds can aim at a specificoverall pharmacological profile of the pharmaceutical preparation. Forexample, a highly potent compound with a shorter duration of action maybe combined with a long-acting compound of lower potency. Theflexibility permitted with respect to the choice of substituents in thecompounds of the formula I allows a great deal of control over thebiological and physico-chemical properties of the compounds and thusallows the selection of such desired compounds. Furthermore, in additionto at least one compound of the formula I and/or a physiologicallytolerable salt and/or its prodrug, the pharmaceutical preparations canalso contain one or more other therapeutically or prophylacticallyactive ingredients.

[0755] When using the compounds of the formula I the dose can varywithin wide limits and, as is customary and is known to the physician,is to be suited to the individual conditions in each individual case. Itdepends, for example, on the specific compound employed, on the natureand severity of the disease to be treated, on the mode and the scheduleof administration, or on whether an acute or chronic condition istreated or whether prophylaxis is carried out. An appropriate dosage canbe established using clinical approaches well known in the medical art.In general, the daily dose for achieving the desired results in an adultweighing about 75 kg is from 0.01 mg/kg to 100 mg/kg, preferably from0.1 mg/kg to 50 mg/kg, in particular from 0. 1 mg/kg to 10 mg/kg, (ineach case in mg per kg of body weight). The daily dose can be divided,in particular in the case of the administration of relatively largeamounts, into several, for example 2, 3 or 4, part administrations. Asusual, depending on individual behavior it may be necessary to deviateupwards or downwards from the daily dose indicated.

[0756] A compound of the formula I can also advantageously be used as ananticoagulant outside an individual. For example, an effective amount ofa compound of the invention can be contacted with a freshly drawn bloodsample to prevent coagulation of the blood sample. Further, a compoundof the formula I or Ib its salts can be used for diagnostic purposes,for example in in vitro diagnoses, and as an auxiliary in biochemicalinvestigations. For example, a compound of the formula I can be used inan assay to identify the presence of factor Xa and/or factor VIIa or toisolate factor Xa and/or factor VIIa in a substantially purified formr.A compound of the invention can be labeled with, for example, aradioisotope, and the labeled compound bound to factor Xa and/or factorVIIa is then detected using a routine method useful for detecting theparticular label. Thus, a compound of the formula I or a salt thereofcan be used as a probe to detect the location or amount of factor Xaand/or factor VIIa activity in vivo, in vitro or ex vivo.

[0757] Furthermore, the compounds of the formula I can be used assynthesis intermediates for the preparation of other compounds, inparticular of other pharmaceutical active ingredients, which areobtainable from the compounds of the formula I, for example byintroduction of substituents or modification of functional groups.

[0758] The general synthetic sequences for preparing the compoundsuseful in the present invention are outlined in the examples givenbelow. Both an explanation of, and the actual procedure for, the variousaspects of the present invention are described where appropriate. Thefollowing examples are intended to be merely illustrative of the presentinvention, and not limiting thereof in either scope or spirit. Thosewith skill in the art will readily understand that known variations ofthe conditions and processes described in the examples can be used tosynthesize the compounds of the present invention.

[0759] It is understood that changes that do not substantially affectthe activity of the various embodiments of this invention are includedwithin the invention disclosed herein. Thus, the following examples areintended to illustrate but not limit the present invention.

EXAMPLES

[0760] When in the final step of the synthesis of a compound an acidsuch as trifluoroacetic acid or acetic acid was used, for example whentrifluoroacetic acid was employed to remove a tBu group or when acompound was purified by chromatography using an eluent which containedsuch an acid, in some cases, depending on the work-up procedure, forexample the details of a freeze-drying process, the compound wasobtained partially or completely in the form of a salt of the acid used,for example in the form of the acetic acid salt or trifluoroacetic acidsalt or hydrochloric acid salt. Abbreviations used: tert-Butyl tBu2,2′-bis(diphenylphoshino-1,1′-binaphthyl BinapBis-(oxo-3-oxazolidinyl)-phosphoryl chloride BOP-Cl dibenzylidenacetonedba Dichloromethane DCM Dicyclohexyl-carbodiimide DCC Diethylphosphorylcyanide DEPC 4-Dimethyaminopyridine DMAP N,N-Dimethylformamide DMFDimethylsulfoxide DMSO 1,1′-Bis(diphenylphosphino)ferrocene DPPFO-(7-Azabenzotriazol-1-yl)-N,N,N′,N′- HATUtetramethyluronium-hexafluorophosphate N-Bromosuccinimide NBSN-Chlorosuccinimide NCS N-Iodosuccinimide NIS N-Ethylmorpholine NEMMethanol MeOH Room temperature 20° C. to 25° C. RT Saturated sat.Tetrahydrofuran THF Trifluoroacetic acid TFAO-((Ethoxycarbonyl)cyanomethyleneamino)- TOTUN,N,N′,N′-tetramethyluronium tetrafluoroborate

Example 1:1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester

[0761] (i) 3-Formyl-1H-indazole-5-carboxylic acid methyl ester

[0762] To a solution of 2 g NaNO₂ in 100 mL THF and 50 mL water, 500 mg1H-Indole-5-carboxylic acid methyl ester were added. The solution wascooled to 0° C. and 7 mL half concentrated hydrochloric acid were addeddropwise. After stirring for 4 days, the reaction mixture was extractedwith ethyl acetate (3×100 mL) and the combined organic layers werewashed with brine (1×50 mL) and dried over MgSO₄. Filtration andevaporation of the solvents under reduced pressure yielded 551 mg crudeproduct which was recrystallized from heptane/ethyl acetate to yield abright yellow solid.

[0763] Yield: 318 mg.

[0764] (ii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-formyl-1H-indazole-5-carboxylicacid methyl ester

[0765] To a solution of 200 mg 3-Formyl-1H-indazole-5-carboxylic acidmethyl ester in 4 mL DMF, 273 mg3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole [prepared by adoptinga procedure described by Ewing, William R.; Becker, Michael R.;Choi-Sledeski, Yong Mi; Pauls, Heinz W.; He, Wei; Condon, Stephen M.;Davis, Roderick S.; Hanney, Barbara A.; Spada, Alfred P.; Burns,Christopher J.; Jiang, John Z.; Li, Aiwen; Myers, Michael R.; Lau, WanF.; Poli, Gregory B; PCT Int. Appl. (2001) 460 pp. WO 0107436 A2] and320 mg Cs₂CO₃ were added and the mixture was stirred at room temperaturefor 1.5 h. This crude reaction mixture was subjected to the subsequentoxidation step.

[0766] (iii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-methyl ester

[0767] To the reaction mixture of the foregoing step 18.7 mL2-Methylbutene (2M in THF) were added at 0° C. Then a solution of 886 mgNaClO₂ (80%) and 940 mg NaH₂PO₄ in 10 mL water was added dropwise. Aftercomplete addition, the reaction mixture was warmed to RT and stirred for2 h. Finally, 4.5 mL half concentrated hydrochloric acid were added andthe mixture was extracted with ethyl acetate (3×100 mL). The combinedorganic layers were washed with brine (1×50 mL) and dried over MgSO₄.Removal of the solvents under reduced pressure yielded the crude productwhich was used in the next reaction step without further purification.

[0768] Yield: 480 mg.

[0769] (i) (1-Isopropyl-piperidin-4-yl)-carbamic acid tert-butyl ester

[0770] To a solution of 5.0 g Piperidin-4-yl-carbamic acid tert-butylester in 15 mL methanol, 7.34 mL acetone, 3.14 g Na(CN)BH₃ and 0.3 mLacetic acid were added. After stirring for 16 h at RT the solvent wasremoved under reduced pressure and the residue was partitioned between30 mL of water and 30 mL of ethyl acetate. The organic layer was washedwith saturated Na₂CO₃ solution, water and then dried over Na₂SO₄.Following filtration, the solvent was removed under reduced pressure toyields a white solid. Yield: 4.8g MS (ES⁺): m/e=243.

[0771] (ii) 1-Isopropyl-piperidin-4-ylamine

[0772] To 4.8 g (1-Isopropyl-piperidin-4-yl)-carbamic acid tert-butylester in 15 mL methanol, 20 mL methanolic hydrochloric acid (8M) wereadded and the mixture was stirred for 16 h. Removal of the solvent underreduced pressure yielded a white solid, which was coevaporated twicewith 20 mL toluene. The product was obtained as its hydrochloride.

[0773] Yield: 5.42 g MS (ES⁺): m/e=143.

[0774] (iv)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester

[0775] To 480 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-methyl ester in 5 mL DCM and 0.6 mL NEt₃, 253 mg1-Isopropyl-piperidin-4-ylamine hydrochloride and 250 mg BOP-Cl wereadded at RT and the mixture was stirred for 3 h. After addition of 20 mLof water the reaction mixture was extracted with ethyl acetate (3×50mL). The combined organic layers were washed with water (1×30) and brine(1×50 mL) and then dried over MgSO₄. After removal of the solvent underreduced pressure the residue was purified by preparative HPLC (C18reverse phase column, elution with a H₂O/MeCN gradient with 0.1% TFA).The fractions containing the product were evaporated and lyophilized toyield a white solid. The product was obtained as its trifluoroacetatesalt. Yield: 210 mg MS (ES⁺): m/e=542, chloro pattern.

[0776] Alternatively1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester was prepared by the following procedure:

[0777] (i) 1H-Indazole-3,5-dicarboxylic acid 5-methyl ester

[0778] To a solution of 5 g 3-Formyl-1H-indazole-5-carboxylic acidmethyl ester in 100 mL acetonitrile and 8 mL DMF a solution of 4.4 gNaH₂PO₄ in 90 mL water was added dropwise at RT within 1 h. Then asolution of 4.2 g NaClO₂ (80%) in 90 mL water followed by 5.3 mL H₂O₂(30%) was added dropwise at 0° C. After stirring for 16 h at RT thereaction mixture was cooled to 0° C. followed by addition of 180 mLhalf-concentrated aqueous hydrochloric acid. The precipitated productwas collected by filtration to yield 2.3 g pure product. The filtratewas extracted with ethyl acetate (3×150 mL), the combined organic layerswere dried over MgSO₄. After removal of the solvent under reducedpressure further 3.42 g of product were obtained. The combined productfractions were used without further purification. Yield: 5.7 g.

[0779] (ii)3-(1-Isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylic acidmethyl ester

[0780] To a solution of 1 g 1H-Indazole-3,5-dicarboxylic acid 5-methylester in 8 mL DCM, 2.5 mL NEt₃, 1.15 g BOP-Cl and 0.98 g1-Isopropyl-piperidin-4-ylamine hydrochloride were added at RT. Themixture was stirred for 3 h. After addition of 20 mL of water thereaction mixture was extracted with DCM (3×50 mL). The combined organiclayers were dried over MgSO₄. After removal of the solvent under reducedpressure the crude product was used without further purification.

[0781] Yield: 1.4 g.

[0782] (iii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester

[0783] To a solution of 1.4 g3-(1-Isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylic acidmethyl ester in 10 mL DMF, 1.42 g Cs₂CO₃ and 1.21 gBromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added at RT andthe reaction mixture was stirred for 2 h. After addition of 10 mL waterthe mixture was extracted with DCM (3×50 mL), the combined organiclayers were dried over MgSO₄ and filtered. Then the solvents wereremoved under reduced pressure and the residue was purified bypreparative HPLC (C18 reverse phase column, elution with a H₂O/MeCNgradient with 0.1% TFA). The fractions containing the product wereevaporated and lyophilized to yield a white solid. The product wasobtained as its trifluoroacetate salt.

[0784] Yield: 2.1 g MS (ES⁺): m/e=542, chloro pattern.

Example 21-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-6-carboxylicacid methyl ester

[0785] The title compound was prepared analogously to example 1 with thedifference that 1H-Indole-6-carboxylic acid methyl ester was usedinstead of 1H-Indole-5-carboxylic acid methyl ester.

[0786] MS (ES⁺): m/e=542, chloro pattern.

Example 31-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-7-carboxylicacid methyl ester

[0787] The title compound was prepared analogously to example 1 with thedifference that 1H-Indole-7-carboxylic acid methyl ester was usedinstead of 1H-Indole-5-carboxylic acid methyl ester.

[0788] MS (ES⁺): m/e=542, chloro pattern.

Example 41-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid

[0789] To a solution of 85 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester in 4 mL THF/water 2:1, 0.8 mL aqueous NaOH (1M) wereadded at RT and the reaction mixture was stirred for 16 h. Then, 2 mLhalf concentrated hydrochloric acid were added and the mixture wasevaporated and lyophilized. The solid residue was stirred with 50 mL DCMand remaining inorganic salts were filtered off. After evaporation ofthe solvent the product was obtained as its hydrochloride.

[0790] Yield: 87 mg MS (ES⁺): m/e=528, chloro pattern.

Example 51-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-7-carboxylicacid

[0791] The title compound was prepared analogously to example 4 with thedifference that1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-7-carboxylicacid methyl ester was used instead of1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester. MS (ES⁺): m/e=528, chloro pattern.

Example 61-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-6-carboxylicacid

[0792] The title compound was prepared analogously to example 4 with thedifference that1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-6-carboxylicacid methyl ester was used instead of1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester. MS (ES⁺): m/e=528, chloro pattern.

Example 7 Indazole-1,3-dicarboxylic acid1-[(5-chloro-pyridin-2-yl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide]

[0793] (i) 1H-Indazole-3-carboxylic acid(1-isopropyl-piperidin-4-yl)-amide

[0794] To a solution of 300 mg 1H-Indazole-3-carboxylic acid in 3 mL DMFand 1 mL NEt₃, 398 mg 1-Isopropyl-piperidin-4-ylamine hydrochloride and471 mg BOP-Cl were added at RT and the mixture was stirred for 16 h.After the addition of 5 mL water the mixture was filtered through a chemelut® cartridge by elution with ethyl acetate and then concentratedunder reduced pressure. The residue was directly subjected to thesubsequent alkylation reaction without further purification. Yield: 340mg.

[0795] (ii) 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide

[0796] To a solution of 5 g 5-Chloro-pyridin-2-ylamine and 1.5 mLpyridine in 30 mL toluene 8 g bromo-acetyl bromide dissolved in 10 mLtoluene was added dropwise under ice cooling. After 2 h the precipitatewas isolated by filtration and recristallized from toluene to yield awhite solid.

[0797] Yield: 12 g.

[0798] (iii) Indazole-1,3-dicarboxylic acid1-[(5-chloro-pyridin-2-yl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide]

[0799] To a solution of 180 mg 1H-Indazole-3-carboxylic acid(1-isopropyl-piperidin-4-yl)-amide in 2 mL DMF, 25 mg NaH (60% in oil)were added at RT and stirred for 10 min. Then, 157 mg2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added and the reactionmixture was allowed to stir for 2 h. After the addition of 2 mL sat.NaHCO₃ the mixture was filtered through a chem elut® cartridge byelution with ethyl acetate and then concentrated under reduced pressure.The residue was purified by preparative HPLC (C18 reverse phase column,elution with a H₂O/MeCN gradient with 0.1% TFA). The fractionscontaining the product were evaporated and lyophilized to yield a whitesolid. The product was obtained as its trifluoroacetate salt.

[0800] Yield: 130 mg MS (ES⁺): m/e=455, chloro pattern.

Example 81-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0801] The title compound was prepared analogously to example 7 with thedifference that 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole wasused instead of 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide. MS (ES⁺):m/e=484, chloro pattern.

Example 91-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 1-ethoxycarbonyloxy-ethyl ester

[0802] To a solution of 0.5 g1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid acetate (see example 4) and 0.529 g 1-chloroethyl-ethylcarbonate in20 mL DMF 0.47 g K₂CO₃ and 0.282 g KI were added and the reactionmixture was stirred for 4h at 60° C. in an argon atmosphere. Afterfiltration and removal of the solvent under reduced pressure the residuewas directly purified by preparative RP-HPLC eluting with a gradient of0-100% acetonitrile in water (+0.01% trifluoroacetic acid). Afteraddition of 1 M hydrochloric acid and lyophilization in anacetonitrile/water mixture, the product was obtained as itshydrochloride.

[0803] Yield: 0.406 g MS (ESI+): m/e=644, chloro pattern.

Example 101-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0804] (i) 3-Formyl-1H-indazole-4-carbonitrile

[0805] The title compound was prepared analogously to example 1 (i) withthe difference that 1H-Indole-4-carbonitrile was used instead of1H-Indole-5-carboxylic acid methyl ester.

[0806] MS (ES⁺): m/e=171.

[0807] (ii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-formyl-1H-indazole-4-carbonitrile

[0808] The title compound was prepared analogously to example 1 (ii)with the difference that 3-Formyl-1H-indazole-4-carbonitrile was usedinstead of 3-Formyl-1H-indazole-5-carboxylic acid methyl ester.

[0809] MS (ES⁺): m/e=368, chloro pattern.

[0810] (iii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-1H-indazole-3-carboxylicacid

[0811] The title compound was prepared analogously to example 1 (iii)with the difference that1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-formyl-1H-indazole-4-carbonitrilewas used instead of1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-formyl-1H-indazole-5-carboxylicacid methyl ester and that a modified oxidation procedure described byE. Dalacanale et al. J. Org. Chem. (1986) 51, 567 employing H₂O₂ insteadof 2-methylbutene was utilized.

[0812] MS (ES⁺): m/e=385, chloro pattern.

[0813] (iv)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0814] The title compound was prepared analogously to example 1 (iv)with the difference that1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-1H-indazole-3-carboxylicacid was used instead of1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-methyl ester. MS (ES⁺): m/e=509, chloro pattern.

Example 111-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0815] (i)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-(N-hydroxycarbamimidoyl)-1H-indazole-3-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide

[0816] To a solution of 200 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide in 3 mL methanol, 27 mgNH₂OH*HCl and 44 mg KOt-Bu were added and the mixture was heated to 50°C. for 3 d. After cooling to RT the precipitated inorganic salts werefiltered off. The precipitate was washed with methanol (2×5 ml) and thecombined filtrates were collected and concentrated under reducedpressure. The residue was subjected to the next reaction step withoutfurther purification. Yield: 223 mg.

[0817] (ii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-(5-oxo4,5-dihydro-[1,2,4]oxadiazol-3-yl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0818] To a solution of 223 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-(N-hydroxycarbamimidoyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide in 2 mL DMF, 35 μl pyridine andi-butylchlorformiate were added at 0° C. Then the reaction mixture waswarmed to RT and stirred for 1 h. After the addition of 2 mL of waterthe mixture was filtered through a chem elut® cartridge by elution withethyl acetate and then concentrated under reduced pressure. The residuewas taken-up in 4 mL xylene and heated to reflux for 3 d. After coolingthe reaction mixture, the solvents were removed under reduced pressure.The residue was purified by preparative HPLC (C18 reverse phase column,elution with a H₂O/MeCN gradient with 0.1% TFA). The fractionscontaining the product were evaporated and lyophilized to yield a whitesolid. The product was obtained as its trifluoroacetate salt.

[0819] Yield: 20.6 mg MS (ES⁺): m/e=568, chloro pattern.

Example 125-(Azetidine-1-carbonyl)-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0820] To a solution of 50 mg1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid in 1 mL DCM 186 mg TOTU and 130 mg NEM were added at RT followed by8.1 mg azetidine. After stirring for 16 h the reaction mixture wasconcentrated under reduced pressure and the residue directly purified bypreparative HPLC (C18 reverse phase column, elution with a H₂O/MeCNgradient with 0.1% TFA). The fractions containing the product wereevaporated and lyophilized to yield a white solid. The product wasobtained as its trifluoroacetate salt.

[0821] Yield: 14 mg MS (ES⁺): m/e=567, chloro pattern.

Example 131-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-methanesulfonyl-ethyl)-amide]

[0822] The title compound was prepared analogously to example 12 withthe difference that 2-Methanesulfonyl-ethylamine was used instead ofazetidine.

[0823] MS (ES⁺): m/e=633, chloro pattern.

Example 141-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-sulfamoyl-ethyl)-amide]

[0824] The title compound was prepared analogously to example 12 withthe difference that 2-Amino-ethanesulfonic acid amide hydrochloride wasused instead of azetidine.

[0825] MS (ES⁺): m/e=634, chloro pattern.

Example 151-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-morpholin-4-yl-ethyl)-amide]

[0826] The title compound was prepared analogously to example 12 withthe difference that 2-Morpholin-4-yl-ethylamine was used instead ofazetidine. MS (ES⁺): m/e=640, chloro pattern.

Example 161-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-trimethylsilanylmethyl-amide

[0827] The title compound was prepared analogously to example 12 withthe difference that C-Trimethylsilanyl-methylamine was used instead ofazetidine.

[0828] MS (ES⁺): m/e=613, chloro pattern.

Example 171-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[bis-(2-hydroxy-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide]

[0829] The title compound was prepared analogously to example 12 withthe difference that 2-(2-Hydroxy-ethylamino)-ethanol was used instead ofazetidine.

[0830] MS (ES⁺): m/e=615, chloro pattern.

Example 181-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2-hydroxy-ethyl)-methyl-amide]3-[(1-isopropyl-piperidin-4-yl)-amide]

[0831] The title compound was prepared analogously to example 12 withthe difference that 2-Methylamino-ethanol was used instead of azetidine.MS (ES⁺): m/e=585, chloro pattern.

Example 19{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-amino}-aceticacid ethyl ester

[0832] The title compound was prepared analogously to example 12 withthe difference that Amino-acetic acid ethyl ester was used instead ofazetidine. MS (ES⁺): m/e=613, chloro pattern.

Example 201-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2,2-difluoro-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide]

[0833] The title compound was prepared analogously to example 12 withthe difference that 2,2-Difluoro-ethylamine was used instead ofazetidine. MS (ES⁺): m/e=591, chloro pattern.

Example 211-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-carbamoylmethyl-amide 3-[(1-isopropyl-piperidin-4-yl)-amide]

[0834] The title compound was prepared analogously to example 12 withthe difference that 2-Amino-acetamide was used instead of azetidine. MS(ES⁺): m/e=584, chloro pattern.

Example 221-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-[(2-hydroxy-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide]

[0835] The title compound was prepared analogously to example 12 withthe difference that 2-Amino-ethanol was used instead of azetidine. MS(ES⁺): m/e=571, chloro pattern.

Example 231-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-{[2-(2-oxo-imidazolidin-1-yl)-ethyl]-amide}

[0836] The title compound was prepared analogously to example 12 withthe difference that 1-(2-Amino-ethyl)-imidazolidin-2-one was usedinstead of azetidine.

[0837] MS (ES⁺): m/e=639, chloro pattern.

Example 241-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide]

[0838] The title compound was prepared analogously to example 12 withthe difference that 2-Amino-2-methyl-propane-1,3-diol was used insteadof azetidine. MS (ES⁺): m/e=615, chloro pattern.

Example 25{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-amino}-aceticacid

[0839] The title compound was prepared analogously to example 12 withthe difference that Amino-acetic acid was used instead of azetidine. MS(ES⁺): m/e=585, chloro pattern.

Example 261-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-(2S)-azetidine-2-carboxylicacid

[0840] The title compound was prepared analogously to example 12 withthe difference that (2S)-Azetidine-2-carboxylic acid was used instead ofazetidine. MS (ES⁺): m/e=611, chloro pattern.

Example 271-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2,2,2-trifluoro-ethyl)-amide]

[0841] The title compound was prepared analogously to example 12 withthe difference that 2,2,2-Trifluoro-ethylamine was used instead ofazetidine. MS (ES⁺): m/e=609, chloro pattern.

Example 28{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-methyl-amino}-aceticacid

[0842] The title compound was prepared analogously to example 12 withthe difference that Methylamino-acetic acid was used instead ofazetidine. MS (ES⁺): m/e=599, chloro pattern.

Example 291-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-hydroxy-ethyl ester

[0843] The title compound was prepared analogously to example 12 withthe difference that Ethane-1,2-diol was used instead of azetidine. MS(ES⁺): m/e=572, chloro pattern.

Example 301-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-([1,4]oxazepane-4-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0844] The title compound was prepared analogously to example 12 withthe difference that [1,4]Oxazepane was used instead of azetidine. MS(ES⁺): m/e=611, chloro pattern.

Example 311-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-hydroxy-azetidine-4-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0845] The title compound was prepared analogously to example 12 withthe difference that Azetidin-3-ol hydrochloride was used instead ofazetidine. MS (ES⁺): m/e=583, chloro pattern.

Example 321-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 3-[(1-isopropyl-piperidin-4-yl)-amide]5-(methoxy-amide)

[0846] The title compound was prepared analogously to example 12 withthe difference that O-Methyl-hydroxylamine was used instead ofazetidine. MS (ES⁺): m/e=557, chloro pattern.

Example 331-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(piperidine-1-carbonyl)-phenyl]-amide

[0847] (i) (4-Amino-phenyl)-piperidin-1-yl-methanone

[0848] To a solution of 100 mg 4-Amino-benzoic acid in 1 mL DCM and 0.2mL NEt₃, 62 mg piperidine and 184 mg BOP-Cl were added at RT and themixture was stirred for 16 h. After the addition of 5 mL water themixture was filtered through a chem elut® cartridge by elution withethyl acetate and then concentrated under reduced pressure. The residuewas directly subjected to the subsequent amide coupling reaction withoutfurther purification. Yield: 125 mg.

[0849] (ii) 1H-Indazole-3-carboxylic acid[4-(piperidine-1-carbonyl)-phenyl]-amide

[0850] To a solution of 100 mg 1H-indazole-3-carboxylic acid in 2 mL DCMand 0.3 mL NEt₃, 125 mg (4-Amino-phenyl)-piperidin-1-yl-methanone and157 mg BOP-Cl were added at RT and the mixture was stirred for 16 h.After the addition of 5 mL water the mixture was filtered through a chemelut® cartridge by elution with ethyl acetate and then concentratedunder reduced pressure. The residue was directly subjected to thesubsequent alkylation reaction without further purification.

[0851] Yield: 112 mg.

[0852] (iii)1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(piperidine-1-carbonyl)-phenyl]-amide

[0853] To a solution of 50 mg 1H-Indazole-3-carboxylic acid[4-(piperidine-l-carbonyl)-phenyl]-amide in 1 mL DMF, 46 mg Cs₂CO₃ and36 mg 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added at RT andthe reaction mixture was stirred for 16 h. After addition of 5 mL waterthe mixture was filtered through a chem elut® cartridge by elution withethyl acetate and and then concentrated under reduced pressure. Theresidue was purified by preparative HPLC (C18 reverse phase column,elution with a H₂O/MeCN gradient with 0.1% TFA). The fractionscontaining the product were evaporated and lyophilized to yield a whitesolid. The product was obtained as its trifluoroacetate salt. Yield: 111mg

[0854] MS (ES⁺): m/e=517, chloro pattern.

Example 341-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(pyrrolidine-1-carbonyl)-phenyl]-amide

[0855] The title compound was prepared analogously to example 33 withthe difference that pyrrolidine andBromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole was used instead ofpiperidine and 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide. MS (ES⁺):m/e=532, chloro pattern.

Example 351-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(morpholine-4-carbonyl)-phenyl]-amide

[0856] The title compound was prepared analogously to example 33 withthe difference that morpholine andBromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole was used instead ofpiperidine and 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide.

[0857] MS (ES⁺): m/e=548, chloro pattern.

Example 361-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(morpholine-4-carbonyl)-phenyl]-amide

[0858] The title compound was prepared analogously to example 33 withthe difference that morpholine was used instead of piperidine. MS (ES⁺):m/e=519, chloro pattern.

Example 371-(1-{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carbonyl}-piperidin-4-yl)-pyrrolidin-2-one

[0859] The title compound was prepared analogously to example 33 withthe difference that 1-Piperidin-4-yl-pyrrolidin-2-one and andBromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole was used instead of(4-Amino-phenyl)-piperidin-1-yl-methanone and2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide. MS (ES⁺): m/e=510, chloropattern.

Example 38N-(5-Chloro-pyridin-2-yl)-2-{3-[4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carbonyl]-indazol-1-yl}-acetamide

[0860] The title compound was prepared analogously to example 33 withthe difference that 1-Piperidin-4-yl-pyrrolidin-2-one and was usedinstead of (4-Amino-phenyl)-piperidin-1-yl-methanone. MS (ES⁺): m/e=481,chloro pattern.

Example 391-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide

[0861] (i) 1-(4-Amino-phenyl)-pyrrolidin-2-one

[0862] 800 mg Benzene-1,4-diamine and 600 μl Dihydro-furan-2-one wereheated for 1 h to 200° C. under microwave irradiation (200 W, CEMDiscover™ apparatus). Finally, 10 mL saturated NaHCO₃ solution wereadded and the mixture was directly purified by chromatography on silicagel eluting with a gradient of DCM/MeOH 100%->50%. The fractionscontaining the product were combined and the solvent evaporated underreduced pressure. Yield: 860 mg.

[0863] (ii) 1H-Indazole-3-carboxylic acid[4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide

[0864] To a solution of 50 mg 1H-Indazole-3-carboxylic acid in 2 mL DCMand 0.2 mL NEt₃, 108 mg 1-(4-Amino-phenyl)-pyrrolidin-2-one and 79 mgBOP-Cl were added at RT and the mixture was stirred for 16 h. After theaddition of 5 mL water the mixture was filtered through a chem elut®cartridge by elution with ethyl acetate and then concentrated underreduced pressure. The residue was directly subjected to the subsequentalkylation reaction without further purification.

[0865] Yield: 140 mg.

[0866] (iii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide

[0867] To a solution of 70 mg 1H-Indazole-3-carboxylic acid[4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide in 1 mL DMF, 9 mg NaH (60% inoil) were added at RT and stirred for 10 min. Then, 61 mgBromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added and thereaction mixture was allowed to stir for 2 h. After the addition of 2 mLsat. NaHCO₃ the mixture was filtered through a chem elut® cartridge byelution with ethyl acetate and then concentrated under reduced pressure.The residue was purified by preparative HPLC (C18 reverse phase column,elution with a H₂O/MeCN gradient with 0.1% TFA). The fractionscontaining the product were evaporated and lyophilized to yield a whitesolid. The product was obtained as its trifluoroacetate salt.

[0868] Yield: 3 mg MS (ES⁺): m/e=518, chloro pattern.

Example 401-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide

[0869] The title compound was prepared analogously to example 39 withthe difference that 2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide was usedinstead of Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole. MS (ES⁺):m/e=489, chloro pattern.

Example 411-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (2′-methanesulfonyl-biphenyl-4-yl)-amide

[0870] The title compound was prepared analogously to example 39 withthe difference that 1-2′-Methanesulfonyl-biphenyl-4-ylamine [prepared byadopting a procedure from Juraszyk, Horst; Dorsch, Dieter; Mederski,Wemer; Tsaklakidis, Christos; Barnes, Christopher; Gleitz, Johannes; PCTInt. Appl. (2001), 37 pp, WO 0170678 A2] was used instead of1-(4-Amino-phenyl)-pyrrolidin-2-one. MS (ES⁺): m/e=589, chloro pattern.

Example 421-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid (2′-methanesulfonyl-biphenyl-4-yl)-amide

[0871] The title compound was prepared analogously to example 39 withthe difference that 1-2′-Methanesulfonyl-biphenyl-4-ylamine [prepared byadopting a procedure from Juraszyk, Horst; Dorsch, Dieter; Mederski,Werner; Tsaklakidis, Christos; Barnes, Christopher; Gleitz, Johannes PCTInt. Appl. (2001), 37 pp, WO 0170678 A2] andBromo-N-(5-chloro-pyridin-2-yl)-acetamide was used instead of1-(4-Amino-phenyl)-pyrrolidin-2-one andBromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole. MS (ES⁺): m/e=560,chloro pattern.

Example 431-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenyl]-amide

[0872] The title compound was prepared analogously to example 8 with thedifference that6-(4-Amino-phenyl)-5-methyl-4,5-dihydro-2H-pyridazin-3-one was usedinstead of 1-Isopropyl-piperidin-4-ylamine hydrochloride. MS (ES⁺):m/e=545, chloro pattern.

Example 441-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (4-morpholin-4-yl-phenyl)-amide

[0873] The title compound was prepared analogously to example 8 with thedifference that 4-Morpholin-4-yl-phenylamine was used instead of1-Isopropyl-piperidin-4-ylamine hydrochloride.

[0874] MS (ES⁺): m/e=520, chloro pattern.

Example 451-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(1H-imidazol-4-yl)-phenyl]-amide

[0875] The title compound was prepared analogously to example 8 with thedifference that 4-(1H-Imidazol-4-yl)-phenylamine was used instead of1-Isopropyl-piperidin-4-ylamine hydrochloride.

[0876] MS (ES⁺): m/e=501, chloro pattern.

Example 461-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (4-piperidin-1-yl-phenyl)-amide

[0877] The title compound was prepared analogously to example 8 with thedifference that 4-Piperidin-1-yl-phenylamine was used instead of1-Isopropyl-piperidin-4-ylamine hydrochloride.

[0878] MS (ES⁺): m/e=518, chloro pattern.

Example 471-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-indazole-5-carboxylicacid methyl ester

[0879] (i) 4-(4-Nitro-phenyl)-morpholine

[0880] A mixture of 24.5 g morpholine and 13.3 g1-Fluoro-4-nitro-benzene in 30 mL DMSO was heated to 100° C. Thissolution was poured on to 300 mL of water and the resulting precipitatewas collected by filtration to yield a bright yellow crystallineproduct, which was dried in vacuo.

[0881] Yield: 19.7 g

[0882] (ii) 4-(4-Nitro-phenyl)-morpholin-3-one

[0883] To a solution of 10 g 4-(4-Nitro-phenyl)-morpholine in 200 mLDCM, 32 g Benzyl-triethyl-ammonium chloride and 22.7 g potassiumpermanganate (325 mesh) were cautiously added at RT. After stirring for1 h the reaction mixture was heated to reflux for 10 h. Then, a solutionof 95 g Na₂SO₃ in 450 mL water was added under ice cooling and vigorousstirring. The mixture was filtered through a pad of celite and thefiltrate was concentrated under reduced pressure. The yellow solid wasstirred with 250 mL water and the precipitated product was collected byfiltration. This crude product was purified by chromatography on silicagel eluting with a gradient of DCM/MeOH 100%->50%. The fractionscontaining the product were combined and the solvent evaporated underreduced pressure. Yield: 2.6 g.

[0884] (iii) 4-(4-Amino-phenyl)-morpholin-3-one

[0885] To a solution of 2.6 g 4-(4-Nitro-phenyl)-morpholin-3-one in 350mL ethyl acetate and 17 mL ethanol 13.2 g SnCl₂ dihydrate were added andthe reaction mixture was heated to reflux for 2 h. Then after cooling toRT the mixture was stirred for 16 h. The precipitated product wascollected by filtration and was pure enough for the next reaction step.Yield: 2.07 g.

[0886] (iv)3-[4-(3-Oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-indazole-5-carboxylicacid methyl ester

[0887] To a solution of 60 mg 1H-Indazole-3,5-dicarboxylic acid 5-methylester and 52 mg 4-(4-Amino-phenyl)-morpholin-3-one in 2 mL DCM, 68 mgBOP-Cl and 0.15 mL NEt₃ were added and the mixture was stirred for 16 hat RT. Then after the reaction mixture was diluted with 20 mL DCM, thesolution was washed with 15 mL of water. The organic phase was driedover MgSO₄ and after filtration concentrated under reduced pressure. Thecrude product was subjected to the next reaction step without furtherpurification. Yield: 71 mg.

[0888] (V)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-indazole-5-carboxylicacid methyl ester

[0889] To a solution of 71 mg3-[4-(3-Oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-indazole-5-carboxylicacid methyl ester in 1.5 mL DMF, 59 mg Cs₂CO₃ and 50 mgBromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added at RT andthe reaction mixture was stirred for 16 h. After filtration the solventswere removed under reduced pressure and residue was purified bypreparative HPLC (C18 reverse phase column, elution with a H₂O/MeCNgradient with 0.1% TFA). The fractions containing the product wereevaporated and lyophilized to yield a white solid. The product wasobtained as its trifluoroacetate salt. Yield: 7.9 mg MS (ES⁺): m/e=592,chloro pattern.

Example 481-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester

[0890] To a solution of 4 g3-(1-Isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylic acidmethyl ester in 35 mL DMF, 3.8 g Cs₂CO₃ and 2.9 g2-Bromo-N-(5-chloro-pyridin-2-yl)-acetamide were added at RT and thereaction mixture was stirred for 2 d. After addition of 50 mL water themixture was extracted with ethyl acetate (3×150 mL), the combinedorganic layers were dried over MgSO₄ and filtered. The solvents wereremoved under reduced pressure and the residue was recrystallized fromdiisopropylether. Yield: 3.8 g MS (ES⁺): m/e=513, chloro pattern.

Example 491-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid

[0891] To a solution of 3.5 g1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester in 150 mL DCM, 31 mL of a 1M solution of borontribromide in DCM were added slowly at RT. The reaction mixture wasstirred for 16 h. concentration of the solution under reduced pressureled to precipitation of the product which was collected by filtration.The product was obtained as its hydrobromide.

[0892] Yield: 4.6 g MS (ES⁺): m/e=499, chloro pattern.

Example 501-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester

[0893] To a solution of 0.6 g1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid acetate and 0.194 g 4-Chloromethyl-5-methyl-[1,3]dioxol-2-one in 30mL DMF 0.424 g K₂CO₃ and 0.254 g KI were added and the reaction mixturewas stirred for 2 h at 50° C. in an argon atmosphere. After filtrationand removal of the solvent under reduced pressure the residue wasdirectly purified by preparative RP-HPLC (two times) eluting with agradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid).After addition of 1 M hydrochloric acid and lyophilization in anacetonitrile/water mixture, the product was obtained as itshydrochloride. Yield: 0.433 g, MS (ESI+): m/e=640, chloro pattern.

Example 511-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(cyanamide-1-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0894] The title compound was prepared analogously to example 12 withthe difference that cyanamide was used instead of azetidine. MS (ES⁺):m/e=552, chloro pattern.

Example 521-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-azetidine-3-carboxylicacid

[0895] The title compound was prepared analogously to example 12 withthe difference that Azetidine-3-carboxylic acid was used instead ofazetidine. MS (ES⁺): m/e=611, chloro pattern.

Example 531-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(3-oxo-morpholin-4-yl)-phenyl]-amide

[0896] The title compound was prepared analogously to example 33 withthe difference that 4-(4-Amino-phenyl)-morpholin-3-one was used insteadof (4-Amino-phenyl)-piperidin-1-yl-methanone. MS (ES⁺): m/e=505, chloropattern.

Example 541-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(4-oxo-4H-pyridin-1-yl)-phenyl]-amide

[0897] (i) 1-(4-Nitro-phenyl)-1H-pyridin-4-one

[0898] A mixture of 10.1 g Pyridin-4-ol and 10 g1-Fluoro-4-nitro-benzene and 46.1 g Cs₂CO₃ in 30 mL DMF was stirred atRT for 2 h. This solution was poured on to 300 mL of water and theresulting precipitate was collected by filtration to yield a brightyellow crystalline product, which was dried in vacuo. Yield: 11.2 g.

[0899] (ii) 1-(4-Amino-phenyl)-1H-pyridin-4-one

[0900] To a solution of 10 g 1-(4-Nitro-phenyl)-H-pyridin-4-one in 510mL ethyl acetate and 26 mL ethanol, 52.1 g SnCl₂ dihydrate were addedand the reaction mixture was heated to reflux for 6 h. Then, aftercooling to RT the solvents were removed under reduced pressure. Theresidue was taken-up in 100 mL aqueous NaHCO₃ solution and 200 mL ethylacetate were added. The inorganic precipitate was filtered off and thesolids were washed with ethyl acetate. After separation of the organiclayer, the aqueous layer of the filtrate was extracted with ethylacetate (2×100 mL) and with DCM (3×150 mL). The combined organic layerswere dried over Na₂SO₄ and the solvents were removed under reducedpressure. The remaining product was pure enough for the next reactionstep.

[0901] Yield: 6 g.

[0902] (iii)1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(4-oxo-4H-pyridin-1-yl)-phenyl]-amide

[0903] The title compound was prepared analogously to example 8 with thedifference that 1-(4-Amino-phenyl)-1H-pyridin-4-one was used instead of1-Isopropyl-piperidin-4-ylamine hydrochloride.

[0904] MS (ES⁺): m/e=528, chloro pattern.

Example 551-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(4-oxo-4H-pyridin-1-yl)-phenyl]-amide

[0905] The title compound was prepared analogously to example 33 withthe difference that 1-(4-Amino-phenyl)-1H-pyridin-4-one was used insteadof (4-Amino-phenyl)-piperidin-1-yl-methanone. MS (ES⁺): m/e=499, chloropattern.

Example 561-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-methoxy-ethyl ester

[0906] The title compound was prepared analogously to example 12 withthe difference that 2-Methoxy-ethanol was used instead of azetidine. MS(ES⁺): m/e=587, chloro pattern.

Example 571-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-hydroxy-ethyl ester

[0907] The title compound was prepared analogously to example 29 withthe difference that1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid was used instead of1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid.

[0908] MS (ES⁺): m/e=544, chloro pattern.

Example 581-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-([1,4]oxazepane-4-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide

[0909] The title compound was prepared analogously to example 30 withthe difference that1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid was used instead of1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid.

[0910] MS (ES⁺): m/e=582, chloro pattern.

[0911] Pharmacological Testing

[0912] The ability of the compounds of the formula I to inhibit factorXa or factor VIIa or other enzymes like thrombin, plasmin, or trypsincan be assessed by determining the concentration of the compound of theformula I that inhibits enzyme activity by 50%, i.e. the IC50 value,which was related to the inhibition constant Ki. Purified enzymes wereused in chromogenic assays. The concentration of inhibitor that causes a50% decrease in the rate of substrate hydrolysis was determined bylinear regression after plotting the relative rates of hydrolysis(compared to the uninhibited control) versus the log of theconcentration of the compound of formula I. For calculating theinhibition constant Ki, the IC50 value was corrected for competitionwith substrate using the formula

Ki=IC50/{1+(substrate concentration/Km)}

[0913] wherein Km is the Michaelis-Menten constant (Chen and Prusoff,Biochem. Pharmacol. 22 (1973), 3099-3108; I. H. Segal, Enzyme Kinetics,1975, John Wiley & Sons, New York, 100-125; which were incorporatedherein by reference).

[0914] a) Factor Xa Assay

[0915] In the assay for determining the inhibition of factor Xa activityTBS-PEG buffer (50 mM Tris-HCl, pH 7.8, 200 mM NaCl, 0.05% (w/v)PEG-8000, 0.02% (w/v) NaN3) was used. The IC50 was determined bycombining in appropriate wells of a Costar half-area microtiter plate 25μl human factor Xa (Enzyme Research Laboratories, Inc.; South Bend,Ind.) in TBS-PEG; 40 μl 10% (v/v) DMSO in TBS-PEG (uninhibited control)or various concentrations of the compound to be tested diluted in 10%(v/v) DMSO in TBS-PEG; and substrate S-2765(N(a)-benzyloxycarbonyl-D-Arg-Gly-L-Arg-p-nitroanilide; Kabi Pharmacia,Inc.; Franklin, Ohio) in TBS-PEG. The assay was performed bypre-incubating the compound of formula I plus enzyme for 10 min. Thenthe assay was initiated by adding substrate to obtain a final volume of100 μl. The initial velocity of chromogenic substrate hydrolysis wasmeasured by the change in absorbance at 405 nm using a Bio-tekInstruments kinetic plate reader (Ceres UV900HDi) at 25° C. during thelinear portion of the time course (usually 1.5 min after addition ofsubstrate). The enzyme concentration was 0.5 nM and substrateconcentration was 140 μM.

[0916] b) Factor VIIa Assay

[0917] The inhibitory activity towards factor VIIa/tissue factoractivity was determined using a chromogenic assay essentially asdescribed previously (J. A. Ostrem et al., Biochemistry 37 (1998)1053-1059 which was incorporated herein by reference). Kinetic assayswere conducted at 25° C. in half-area microtiter plates (Costar Corp.,Cambridge, Mass.) using a kinetic plate reader (Molecular DevicesSpectramax 250). A typical assay consisted of 25 μl human factor VIIaand TF (5 nM and 10 nM, respective final concentration) combined with 40μl of inhibitor dilutions in 10% DMSO/TBS-G PEG buffer (50 mM Tris, 15mM NaCl, 5 mM CaCl₂, 0.05% PEG 8000, pH 8.15). Following a 15 minutespreincubation period, the assay was initiated by the addition of 35 μlof the chromogenic substrate S-2288 (D-Ile-Pro-Arg-p-nitroanilide,Pharmacia Hepar Inc., 500 μM final concentration). The results(inhibition constants Ki (FXa) for inhibition of factor Xa) are shown inTable 1. TABLE 1 Example Ki(FXa) [nM]  1  79  2  35  3  17  4  18  5 285 6 212  7  86  8  6  9  82 10  9 11  7 12  5 13  40 14  28 15  46 16  5417  30 18  13 19  26 20  47 21  33 22  28 23  33 24  51 25  14 26  17 27 39 28  15 29  39 30  12 32  22 34 120 35 530 37 210 39  19 41  7 43 73045 180 47  9 50  41 51  5 52  10 53 240 54  52 56  43

We claim:
 1. A compound of formula I,

wherein one of J₁ and J₂ is N, and the other is N—Q—R⁰; R⁰ is 1) amonocyclic or bicyclic 6- to 14-membered aryl, wherein the aryl ismono-, di- or trisubstituted independently of one another by R8, 2) amonocyclic or bicyclic 4- to 15-membered heterocyclyl selected from thegroup consisting of benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl,benzoxazolyl, benzothiazolyl, benzothiophenyl, cinnolinyl, chromanyl,indazolyl, indolyl, isochrornanyl, isoindolyl, isoquinolinyl,phenylpyridyl, phthalazinyl, pteridinyl, purinyl, pyridyl,pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, pyrimidinyl,quinazolinyl, quinolyl, quinoxalinyl or 1,4,5,6-tetrahydro-pyridazinyl,wherein the heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8, or 3) a monocyclic orbicyclic 4- to 15-membered heterocyclyl, containing one, two, three orfour heteroatoms chosen from nitrogen, sulfur or oxygen, wherein saidheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R8, and which is additionallysubstituted by a monocyclic or bicyclic 4- to 15-membered heterocyclyl,containing one, two, three or four heteroatoms chosen from nitrogen,sulfur or oxygen, wherein heterocyclyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R8; R8 is 1) halogen, 2)—NO₂, 3) —CN, 4) —C(O)—NH₂, 5) —OH, 6) —NH₂, 7) —O—CF₃ 8) a monocyclicor bicyclic 6- to 14-membered aryl, wherein the aryl is mono-, di- ortrisubstituted independently of one another by halogen or—O—(C₁-C₈)-alkyl, 9) —(C₁-C₈)-alkyl, wherein alkyl is unsubstituted ormono-, di- or tri-substituted independently of one another by halogen,NH₂, —OH or methoxy, 10) —O—(C₁-C₈)-alkyl, wherein alkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by halogen, NH₂, —OH or methoxy, 11) —SO₂—CH₃ or 12) —SO₂—CF₃,provided that when R⁰ is a monocyclic or bicyclic 6- to 14-memberedaryl, then R8 is at least one halogen, —C(O)—NH₂ or —O—(C₁-C₈)-alkyl;the substructure

 in formula I is a 4-to 8 membered saturated, partially unsaturated oraromatic cyclic group containing zero, 1, 2, 3 or 4 heteroatoms chosenfrom nitrogen, sulfur or oxygen and is un-substituted or substituted 1,2, 3, 4, 5 or 6 times by R3 or substituted 1 or 2 times by ═O; Q is adirect bond, —(C₀-C₂)-alkylene-C(O)—NR¹⁰—, —NR¹⁰—C(O)—NR¹⁰—,—NR¹⁰—C(O)—, —SO₂—, —(C₁-C₆)-alkylene,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—S—(CH₂)_(n)—, —(CH₂)_(m)—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—CH(OH)—(CH₂)_(n)—,—(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)—,—(C₂-C₃)-alkylene-O—(C₀-C₃)-alkylene-, —(C₂-C₃)-alkylene-S(O)—,—(C₂-C₃)-alkylene-S(O)₂—, —(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—,—(C₂-C₃)-alkylene-S(O)₂—NH—(R¹⁰)—, —(C₂-C₃)-alkylene-N(R¹⁰)— or—(C₀-C₃)-alkylene-C(O)—O—(CH₂)_(m)—, wherein —(CH₂)_(m)— or —(CH₂)_(n)—are alkylene that is unsubstituted or mono-, di- or trisubstitutedindependently of one another by halogen, —NH₂ or —OH, or—(C₃-C₆)-cycloalkylene, that is unsubstituted or mono-, di- ortrisubstituted independently of one another by halogen, —NH₂ or —OH; R¹is hydrogen, —(C₁-C₄)-alkyl, wherein the alkyl is unsubstituted orsubstituted one to three times by R13, —(C₁-C₃)-alkylene-C(O)—NH—R⁰,—(C₁-C₃)-alkylene-C(O)—O—R¹⁵, a monocyclic or bicyclic 6- to 14-memberedaryl, wherein the aryl is mono-, di- or trisubstituted independently ofone another by R8, a monocyclic or bicyclic 4- to 15-memberedheterocyclyl, containing one, two, three or four heteroatoms chosen fromnitrogen, sulfur or oxygen, —(C₁-C₃)-perfluoroalkylene,—(C₁-C₃)-alkylene-S(O)—(C₁-C₄)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—(C₁-C₃)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—N(R^(4′))—R^(5′),—(C₁-C₃)-alkylene-O—(C₁-C₄)-alkyl, —(C₀-C₃)-alkylene-(C₃-C₈)-cycloalkyl,or —(C₀-C₃)-alkylene-het, wherein the het is a 3- to 7-membered cyclicresidue, containing up to 1, 2, 3 or 4 heteroatoms chosen from nitrogen,sulfur or oxygen, wherein said cyclic residue is unsubstituted or mono-,di- or trisubstituted independently of one another by R14; R^(4′) andR^(5′) are independent of one another are identical or different and arehydrogen or —(C₁-C₄)-alkyl, R² is a direct bond or —(C₁-C₄)-alkylene, orR¹ and R³ together with the atoms to which they are bonded form a 6- to8-membered cyclic group, containing 1, 2, 3 or 4 heteroatoms chosen fromnitrogen, sulfur or oxygen, wherein said cyclic group is unsubstitutedor mono-, di- or trisubstituted independently of one another by R14, orR¹—N—R²—V form a 4- to 8-membered cyclic group, containing 1, 2, 3 or 4heteroatoms chosen from nitrogen, sulfur or oxygen, wherein said cyclicgroup is unsubstituted or mono-, di- or trisubstituted independently ofone another by R14; R14 is halogen, —OH, ═O, —(C₁-C₈)-alkyl,—(C₁-C₄)-alkoxy, —NO₂, —C(O)—OH, —CN, —NH₂, —C(O)—O—(C₁-C₄)-alkyl,—(C₀-C₈)-alkyl-SO₂—(C₁-C₄)-alkyl,—(C₀-C₈)-alkyl-SO₂—(C₁-C₃)-perfluoroalkyl,—(C₀-C₈)-alkyl-SO₂—N(R¹⁸)—R²¹, —C(O)—NH—(C₁-C₈)-alkyl,—C(O)—N—[(C₁-C₈)-alkyl]₂, —NR¹⁸—C(O)—NH—(C₁-C₈)-alkyl, —C(O)—NH₂,—S—R¹⁸, or —NR¹⁸—C(O)—NH—[(C₁-C₈)-alkyl]₂, wherein R¹⁸ and R²¹ areindependently from each other hydrogen, —(C₁-C₃)-perfluoroalkyl or—(C₁-C₆)-alkyl; V is 1) a 3- to 7-membered cyclic residue, containing 1,2, 3 or 4 heteroatoms chosen from nitrogen, sulfur or oxygen, whereinsaid cyclic residue is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14, 2) a 6- to 14-membered aryl,wherein the aryl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14, or 3) a monocyclic or bicyclic 4-to 15-membered heterocyclyl, wherein the heterocyclyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R14, Gis a direct bond, —(CH₂)_(m)—NR¹⁰—SO₂—NR¹⁰—(CH₂)_(n)—,—(CH₂)_(m)—CH(OH)—(CH₂)_(n)—, —(CH₂)_(m)—, —(CH₂)_(m)—O—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—C(O)—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—C(O)—(CH₂)_(n)—,—(CH₂)_(m)—C(O)—(CH₂)_(n)—, —(CH₂)—S—(CH₂)_(n)—,—(CH₂)_(m)—SO₂—NR¹⁰—(CH₂)_(n)—, —(CH₂)_(m)—NR¹⁰—SO₂—(CH₂)_(n)—,—(CH₂)_(m)—NR¹⁰—, —(CH₂)_(m)—O—C(O)—NR¹⁰—(CH₂)_(n)— or—(CH₂)_(m)—NR¹⁰—C(O)—O—(CH₂)_(n)—; n and m are independently of oneanother identical or different and are the integers zero, 1, 2, 3, 4, 5or 6; M is 1) hydrogen, 2) —(C₁-C₈)-alkyl, wherein the alkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14, 3) —C(O)—N(R11)—R12, 4) —(CH₂)_(m)—NR¹⁰, 5) a 6- to14-membered aryl, wherein the aryl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14, 6) a monocyclic orbicyclic 4- to 15-membered heterocyclyl, wherein the heterocyclyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14, 7) —(C₃-C₈)-cycloalkyl, wherein the cycloalkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14, or 8) a 3- to 7-membered cyclic residue, containing 1,2, 3 or 4 heteroatoms chosen from nitrogen, sulfuir or oxygen, whereinthe cyclic residue is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14; R3 is 1) hydrogen, 2) halogen, 3)—(C₁-C₄)-alkyl, wherein the alkyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13, 4)—(C₁-C₃)-perfluoroalkyl, 5) phenyl, wherein the phenyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R13, 6)—(C₀-C₄)-alkylene-O—R19, 7) —NO₂, 8) —CN, 9) —SO_(s)—R¹¹, wherein s is 1or 2, 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2, 11)—(C₀-C₄)-alkylene-C(O)—R¹¹, 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹, 13)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹², 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹², 15)—NR¹⁰—SO₂—R¹⁰, 16) —S—R¹⁰, 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl, 18)—C(O)—O—C(R15, R16)—O—C(O)—R17, 19)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl, 20)—C(O)—O—C(R15, R16)—O—C(O)—O—R17, 21) —(C₀-C₄)-alkylene-(C₆-C₁₄)-aryl,wherein the aryl is mono-, di- or trisubstituted independently of oneanother by R13, 22) —(C₀-C₄)-alkylene-(C₄-C₁₅)-heterocyclyl, wherein theheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R13 23)—(C₀-C₄)-alkylene-(C₃-C₈)-cycloalkyl, wherein cycloalkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13, 24) —(C₀-C₄)-alkylene-het, wherein het is unsubstitutedor mono-, di- or trisubstituted independently of one another by R13, 25)—(C₀-C₄)-alkylene-O—CH₂—(C₁-C₃)-perfluoroalkylene-CH₂—O—(C₀-C₄)-alkyl,26) —SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2, 27)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³, 28) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or29) a residue selected from the group consisting of

wherein Me is methyl; R19 is a) hydrogen, b) —(C₁-C₄)-alkyl, whereinalkyl is unsubstituted or mono-, di- or trisubstituted independently ofone another by R13, or c) phenyl, wherein the phenyl is unsubstituted ormono-, di- or trisubstituted independently of one another by R13, d)—CF₃, or e) —CHF₂, or two —OR19 residues and adjacent atoms throughwhich they are attached form together with the atoms which they areattached to a 5- or 6-membered ring, which is unsubstituted orsubstituted one, two, three or four times by R13; R11 and R12 areindependently of one another identical or different and are 1) hydrogen,2) —(C₁-C₆)-alkyl, wherein the alkyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13, 3)—(C₀-C₆)-alkyl-(C₃-C₈)-cycloalkyl, 4) —SO_(t)—R¹⁰, wherein t is 1 or 2,5) —(C₀-C₆)-alkyl-(C₆-C₁₄)-aryl, wherein the alkyl and arylindependently from one another are unsubstituted or mono-, di- ortrisubstituted by R13, 6) —(C₁-C₃)-perfluoroalkyl, 7) —O—R¹⁷, or 8)—(C₀-C₆)-alkyl-(C₄-C₁₅)-heterocyclyl, wherein alkyl and heterocyclylindependently from one another are unsubstituted or mono-, di- ortrisubstituted by R13, or R11 and R12 together with the nitrogen atom towhich they are bonded can form a 4- to 8-membered monocyclicheterocyclic ring which in addition to the nitrogen atom can contain oneor two identical or different ring heteroatoms chosen from oxygen,sulfur and nitrogen; wherein said heterocyclic ring is unsubstituted ormono-, di- or trisubstituted independently of one another by R13; R13 ishalogen, —NO₂, —CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰, —C(O)—N(R¹⁰)—R²⁰,—N(R¹⁰)—R²⁰, —(C₃-C₈)-cycloalkyl, —(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃,—N(R¹⁰)—S(O)_(u)—R¹⁰, wherein u is 1 or 2, —S—R¹⁰, —SO_(r)—R¹⁰, whereinr is 1 or 2, —S(O)_(v)—N(R¹⁰)—R²⁰, wherein v is 1 or 2, —C(O)—R¹⁰,—(C₁-C₈)-alkyl, —(C₁-C₈)-alkoxy, phenyl, phenyloxy, —O—CF₃,—(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—R17, —(C₁-C₄)-alkoxy-phenyl,—(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—O—R17, —(C₁-C₃)-perfluoroalkyl,—O—R15, —NH—C(O)—NH—R¹⁰, —NH—C(O)—O—R¹⁰, or a residue from the groupconsisting of

wherein Me is methyl; R¹⁰ and R²⁰ are independently of one anotherhydrogen, —(C₁-C₆)-alkyl, —(C₀-C₄)-alkyl-OH,—(C₀-C₄)-alkyl-O—(C₁-C₄)-alkyl or —(C₁-C₃)-perfluoroalkyl; R15 and R16are independently of one another hydrogen, —(C₁-C₆)-alkyl, or togetherwith the carbon atom to which they are bonded they can form a 3- to 6membered carbocyclic ring which is unsubstituted or substituted one tothree times by R¹⁰; and R17 is —(C₁-C₆)-alkyl, —(C₁-C₆)-alkyl-OH,—(C₁-C₆)-alkyl-O—(C₁-C₆)-alkyl, —(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-O—(C₁-C₈)-alkyl-(C₃-C₈)-cycloalkyl,—(C₁-C₆)-alkyl-(C₃-C₈)-cycloalkyl, wherein the cycloalkyl isunsubstituted or substituted one, two or three times by —OH,—O—(C₁-C₄)-alkyl or R¹⁰; or a stereoisomer or a mixture of stereoisomersthereof in any ratio, or a physiologically tolerable salt thereof. 2.The compound according to claim 1, wherein substructure D is a 5-to 6membered saturated, partially unsaturated or aromatic cyclic groupcontaining zero, 1, 2, 3 or 4 heteroatoms chosen from nitrogen, sulfuror oxygen and is substituted 1, 2, 3, 4, 5 or 6 times by R3; R3 as 25)is—(C₀-C₃)-alkylene-O—CH₂-(C₁-C₃)-perfluoroalkylene-CH₂—O—(C₀-C₃)-alkyl;and R¹⁰ and R²⁰ are independently of one another hydrogen,—(C₁-C₆)-alkyl or —(C₁-C₃)-perfluoroalkyl;
 3. The compound according toclaim 1, wherein R⁰ as 1) is phenyl, naphthyl, biphenylyl, anthryl orfluorenyl, each of which is mono-, di- or trisubstituted independentlyof one another by R8, or 3) is acridinyl, azabenzimidazolyl,azaspirodecanyl, azepinyl, azetidinyl, aziridinyl, benzimidazolyl,benzofuranyl, benzothiofuiranyl, benzothiophenyl, benzoxazolyl,benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl,benzisothiazolyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl,chromenyl, cinnolinyl, decahydrochinolinyl, 4,5-dihydrooxa-zolinyl,dioxazolyl, dioxazinyl, 1,3-dioxolanyl, 1,3-dioxolenyl,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl,furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl,indolinyl, indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl,isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl,isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl,isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl,morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl,1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl,oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl,4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl,tetrahydroisoquinolinyl, tetrahydroquinolinyl,1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl,1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl or xanthenyl, each ofwhich is unsubstituted or mono-, di- or trisubstituted independently ofone another by R8, and which is additionally substituted by aheterocyclyl selected from the group consisting of acridinyl,azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl,benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl,benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl,benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl,carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydrochinolinyl,4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl,1,3-dioxolenyl, 6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl,imidazolidinyl, imidazolinyl, imnidazolyl, 1H-indazolyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl,isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl,isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl,naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,2-oxazinyl,1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl,phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl,4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl,tetrahydroisoquinolinyl, tetrahydroquinolinyl,1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, thiophenolyl, thiophenyl, thiopyranyl,1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl and xanthenyl, whereinthe heterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R8; substructure D is a residue selectedfrom the group consisting of azetidine, azetine, azocane, azocane-2-one,cyclobutyl, cyclooctane, cyclooctene, cyclopentyl, cyclohexyl,cycloheptyl, cyclooctyl, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, [1,4]diazocane, [1,2]diazocan-3-one, [1,3]diazocan-2-one,dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane, furan,imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine,isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline,ketopiperazine, morpholine, 1,2-oxa-thiepane, 1,2-oxathiolan,1,2-oxazine, 1,3-oxazine, 1,4-oxazine, oxazole, [1,4]oxazocane,[1,3]oxazocan-2-one, oxetan, oxocane, oxocan-2-one, piperazine,piperidine, phenyl, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, 5,6,7,8-tetrahydro-1H-azocin-2-one, tetrahydrofuran,tetrahydropyran, tetrahydropyridine, tetrazine, thiadiazine,thiadiazole, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole,thiazole, thiazolidine, thiazoline, thietan, thiocane,thiocane-1,1-dioxide, thiocane-1-oxide, thiocan-2-one, thiomorpholine,thiophene, thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole and 1,2,4-triazole, and is unsubstituted or substituted1, 2, 3, 4, 5 or 6 times by R3; R¹ as a monocyclic or bicyclic 6- to14-membered aryl is phenyl, naphthyl, biphenylyl, anthryl or fluorenyl,each of which is mono-, di- or trisubstituted independently of oneanother by R8, or —(C₀-C₃)-alkylene-het, wherein the het is a residueselected from the group concsisting of azepine, azetidine, aziridine,azirine, 1,4-diazapane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine,diaziridine, diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxolene,1,3-dioxolane, furan, imidazole, imidazoline, imidazolidine,isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline,isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, 1,4-oxazepane,1,2-oxa-thiepane, 1,2-oxathiolane, 1,2-oxazine, 1,3-oxazine,1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine, piperidine,pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine,pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline,tetrahydropyridine, tetrazine, tetrazole, thiadiazine thiadiazole,1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole,thiazolidine, thiazoline, thienyl, thietan, thiomorpholine, thiopyran,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole and1,2,4-triazole, wherein the het is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14, or R¹ and R3together with the atoms to which they are bonded form azocane,azocane-2-one, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine,[1,4]diazocane, [1,2]diazocan-3-one, [1,3]diazocan-2-one, dioxazine,[1,4]dioxocane, dioxole, ketopiperazine, morpholine, 1,2-oxazine,1,3-oxazine, 1,4-oxazine, [oxocane, oxocan-2-one, piperazine,piperidine, pyran, pyrazine, pyridazine, pyrimidine or5,6,7,8-tetrahydro-1H-azocin-2-one, each of which is unsubstituted ormono-, di- or trisubstituted independently of one another by R14, orR¹—N—R²—V form azepine, azetidine, dioxazole, dioxazine, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine,isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline,isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine, oxazole,piperazine, piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiazole,thiadiazole, thiazolidine, thiazoline, thiomorpholine, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, eachof which is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R14; V is 2) phenyl, naphthyl, biphenylyl, anthryl orfluorenyl, each of which is mono-, di- or trisubstituted independentlyof one another by R14, or 3) acridinyl, azaindole (1H-pyrrolopyridine),azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl,benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl,benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl,benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl,carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydrochinolinyl,1,4-diazepane, 4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl,1,3-dioxolanyl, 1,3-dioxolenyl, 6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl,imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl,isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl,isothiazolidinyl, isothiazolinyl, isoxazolyl, isoxazolinyl,isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl, morpholinyl,naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl,1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl, 1,2-oxazinyl,1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl, oxazolyl,phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl,4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuiranyl,tetrahydroisochinolinyl, tetrahydrochinolinyl,1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl,1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl or xanthenyl, each of which is unsubstituted or mono-,di- or trisubstituted independently of one another by R14; M is 1)hydrogen, 2) —(C₁-C₈)-alkyl, wherein the alkyl is unsubstituted ormono-, di- or trisubstituted independently of one another by R14, 3)—C(O)—N(R11)—R12, 4) —(CH₂)_(m)—NR¹⁰, 5) —(C₆-C₁₄)-aryl, wherein thearyl is unsubstituted or mono-, di- or trisubstituted independently ofone another by R14, 6) —(C₄-C₁₅)-heterocyclyl, wherein the heterocyclylis unsubstituted or mono-, di- or trisubstituted independently of oneanother by R14, or 7) —(C₃-C₈)-cycloalkyl, wherein the cycloalkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14; R3 as 25) is—(C₀-C₃)-alkylene-O—CH₂—(C₁-C₃)-perfluoroalkylene-CH₂—O—(C₀-C₃)-alkyl,two —OR19 residues and adjacent atoms through which they are attachedmay form together a 1,3-dioxole ring or a 2,3-dihydro-[1,4]dioxine ring,which is substituted one, two, three or four times by R13; R11 and R12together with the nitrogen atom to which they are bonded may formazepine, azetidine, dioxazole, dioxazine, 1,4-diazepane, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine,isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline,isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine,[1,4]oxazepane, oxazole, piperazine, piperidine, pyrazine, pyrazole,pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole,pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine,tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline,thiomorpholine, thiophene, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, each of which isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13; and R15 and R16 are independently of one anotherhydrogen, —(C₁-C₆)-alkyl, or together with the carbon atom to which theyare bonded forrn cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl,wherein each ring is unsubstituted or substituted one to three times byR¹⁰.
 4. The compound according to claim 1, wherein R⁰ as 1) is phenyl,naphthyl, biphenyl, anthryl or fluorenyl, each of which is mono-, di- ortrisubstituted independently of one another by R8, or 3) isazabenzimidazolyl, benzimidazolyl, 1,3-benzodioxolyl, benzofuranyl,benzothiazolyl, benzothiophenyl, benzoxazolyl, chromanyl, cinnolinyl,2-furyl, 3-furyl; imidazolyl, indolyl, indazolyl, isochromanyl,isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl,phthalazinyl, pteridinyl, purinyl, pyrazinyl, pyrazolyl, pyridazinyl,pyridoimidazolyl, pyridopyridinyl, pyridopyrimidinyl, 2-pyridyl,3-pyridyl, 4-pyridyl, pyrimidinyl, pyrrolyl; 2-pyrrolyl, 3-pyrrolyl,quinolinyl, quinazolinyl, quinoxalinyl, tetrazolyl, thiazolyl, 2-thienylor 3-thienyl, each of which is additionally substituted by aheterocyclyl selected from the group consisting of acridinyl,azabenzimidazolyl, azaspirodecanyl, azepinyl, azetidinyl, aziridinyl,benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl,benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl,benzisoxazolyl, benzisothiazolyl, carbazolyl, 4aH-carbazolyl,carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydrochinolinyl,4,5-dihydrooxa-zolinyl, dioxazolyl, dioxazinyl, 1,3-dioxolanyl,1,3-dioxolenyl, 6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]-tetrahydrofuranyl, furanyl, furazanyl,imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolinyl,indolizinyl, indolyl, 3H-indolyl, isobenzofuranyl, isochromanyl,isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl),isothiazolyl, isothiazolidinyl, isothiazolinyl, isoxazolyl,isoxazolinyl, isoxazolidinyl, 2-isoxazolinyl, ketopiperazinyl,morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, 1,2-oxa-thiepanyl, 1,2-oxathiolanyl, 1,4-oxazepanyl,1,2-oxazinyl, 1,3-oxazinyl, 1,4-oxazinyl, oxazolidinyl, oxazolinyl,oxazolyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl,pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl,pyrazolyl, pyridazinyl, pyridooxazolyl, pyridoimidazolyl,pyridothiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolidinonyl,pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl,4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl,tetrahydroisochinolinyl, tetrahydrochinolinyl,1,4,5,6-tetrahydro-pyridazinyl, tetrahydropyridinyl,tetrahydrothiophenyl, tetrazinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl,1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl,1,3,4-thiadiazolyl, thianthrenyl, 1,2-thiazinyl, 1,3-thiazinyl,1,4-thiazinyl, 1,3-thiazolyl, thiazolyl, thiazolidinyl, thiazolinyl,thienyl, thietanyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl,thietanyl, thiomorpholinyl, thiophenyl, thiopyranyl, 1,2,3-triazinyl,1,2,3-triazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl and xanthenyl, wherein the heterocyclyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R8; R8as 1) is F, Cl, or Br; substructure D is a residue selected from thegroup consisting of phenyl, pyridyl, pyridyl-N-oxide pyridyl, pyrrolyl,furyl, thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl,triazolyl, isothiazolyl, thiadiazolyl, pyrimidinyl, pyridazinyl, andpyrazinyl, and is unsubstituted or substituted 1, 2, 3 or 4 times by R3;Q is a direct bond, —(C₀-C₂)-alkylene-C(O)—NR¹⁰—, —NR¹⁰—C(O)—NR¹⁰—,—NR¹⁰—C(O)—, —SO₂— or —(C₁-C₆)-alkylene or—(C₀-C₃)-alkylene-C(O)—O—(C₀-C₂)-alkylene; R¹ is hydrogen,—(C₁-C₄)-alkyl, wherein the alkyl is unsubstituted or substituted one tothree times by R13, —(C₁-C₃)-alkylene-C(O)—NH—R⁰,—(C₁-C₃)-alkylene-C(O)—O—R¹⁵, —(C₁-C₃)-perfluoroalkylene,—(C₁-C₃)-alkylene-S(O)—(C₁-C₄)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—(C₁-C₃)-alkyl,—(C₁-C₃)-alkylene-S(O)₂—N(R^(4′))—R^(5′),—(C₁-C₃)-alkylene-O—(C₁-C₄)-alkyl, —(C₀-C₃)-alkylene-(C₃-C₈)-cycloalkyl,or —(C₀-C₃)-alkylene-het, wherein the het is azepine, azetidine,aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, diaziridine, diazirine, dioxazole, dioxazine, dioxole,1,3-dioxolene, 1,3-dioxolane, furan, imnidazole, imidazoline,imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole,isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine,1,2-oxa-thiepane, 1,2-oxathiolane, 1,4-oxazepane, 1,2-oxazine,1,3-oxazine, 1,4-oxazine, oxazole, oxaziridine, oxirane, piperazine,piperidine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone,pyrroline, tetrahydropyridine, tetrazine, tetrazole, thiadiazinethiadiazole, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, 1,3-thiazole,thiazole, thiazolidine, thiazoline, thienyl, thietan, thiomorpholine,thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole or 1,2,4-triazole, each of which is unsubstituted ormono-, di- or trisubstituted independently of one another by R14, orR¹—N—R²—V form azepine, azetidine, 1,4-diazepane, dioxazole, dioxazine,1,2-diazepine, 1,3-diazepine, 1,4-diazepine, imidazole, imidazoline,imidazolidine, isothiazole, isothiazolidine, isothiazoline, isoxazole,isoxazoline, isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine,1,4-oxazepane, oxazole, piperazine, piperidine, pyrazine, pyrazole,pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole,pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine,tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline,thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole or 1,2,4-triazole, each of which is unsubstituted ormono-, di- or trisubstituted independently of one another by R14; V is2) phenyl, wherein the phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14, or 3) azaindole(1H-pyrrolopyridine), azepine, azetidine, aziridine, azirine,1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, diaziridine,diazirine, dioxazole, dioxazine, dioxole, 1,3-dioxolene, 1,3-dioxolane,furan, imidazole, imidazoline, imidazolidine, isothiazole,isothiazolidine, isothiazoline, isoxazole, isoxazoline, isoxazolidine,2-isoxazoline, ketopiperazine, morpholine, 1,2-oxa-thiepane,1,2-oxathiolane, 1,4-oxazepane, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine,oxazole, oxaziridine, oxirane, piperazine, piperidine, pyran, pyrazine,pyrazole, pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine,pyrrole, pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine,tetrazine, tetrazole, thiadiazine, thiadiazole, 1,2-thiazine,1,3-thiazine, 1,4-thiazine, 1,3-thiazole, thiazole, thiazolidine,thiazoline, thienyl, thietan, thiomorpholine, thiopyran, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, eachof which is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R14; M is 1) hydrogen, 2) —(C₁-C₈)-alkyl, wherein thealkyl is unsubstituted or mono-, di- or trisubstituted independently ofone another by R14, 3) —C(O)—N(R11)—R12, 4) —(CH₂)_(m)—NR¹⁰, 5) phenylor naphthyl, wherein the phenyl or naphthyl are unsubstituted or mono-,di- or trisubstituted independently of one another by R14, 6)(C₄-C₁₅)-heterocyclyl, wherein the heterocyclyl is selected from thegroup consisting of azepane, azepine, 1,4-diazepane, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, imidazole, isothiazole, isoxazole,isoxazolidine, 2-isoxazoline, ketomorpholine, ketopiperazine,morpholine, oxazole, [1,4]-oxazepane, piperazine, piperazinone,piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine,pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran,1,4,5,6-tetrahydro-pyridazinyl, tetrazine, tetrazole, thiadiazole,thiazole, thiophene, thiomorpholine, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,3-triazole and 1,2,4-triazole, wherein theheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14, or 7) —(C₃-C₈)-cycloalkyl, whereinthe cycloalkyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14; R3 is 1) hydrogen, 2) halogen, 3)—(C₁-C₄)-alkyl, wherein the alkyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13, 4)—(C₁-C₃)-perfluoroalkyl, 5) phenyl, wherein the phenyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R13, 6)—(C₀-C₄)-alkylene-O—R19, 8) —CN, 9) —SO_(s)—R¹¹, wherein s is 1 or 2,10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2, 11)—(C₀-C₄)-alkylene-C(O)—R¹¹, 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹, 13)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹², 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹², 15)—NR¹⁰—SO₂—R¹⁰, 17)—(C₀-C₂)-alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl, 18)—C(O)—O—C(R15, R16)—O—C(O)—R17, 19)—(C₀-C₂)-alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl, 20)—C(O)—O—C(R15, R16)—O—C(O)—O—R17, 21) —(C₀-C₄)-alkylene-(C₆-C₁₄)-aryl,wherein aryl is as defined above and is mono-, di- or trisubstitutedindependently of one another by R13, 22)—(C₀-C₄)-alkylene-(C₄-C₁₅)-heterocyclyl, wherein the heterocyclyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13, 23) —(C₀-C₄)-alkylene-(C₃-C₈)-cycloalkyl, whereincycloalkyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R13, 24) —(C₀-C₄)-alkylene-het, whereinthe het is as defined above and is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13, 25)—(C₀-C₃)-alkylene-O—CH₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,—(C₀-C₃)-alkylene-O—CH₂—CF₂—CF₂—CH₂—O—(C₀-C₃)-alkyl, or—(C₀-C₃)-alkylene-O—CH₂—(C₁-C₃)-perfluoroalkylene-CH₂—OH, 26)—SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2, 27)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³, 28) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or29) a residue selected from the group consisting of

 wherein Me is methyl; two —OR19 residues and adjacent atoms throughwhich thay are attached may form together a 1,3-dioxole ring or a2,3-dihydro-[1,4]dioxine ring, each of which is substituted one, two,three or four times by R13; R11 and R12 are independently of one anotheridentical or different and are 1) hydrogen, 2) —(C₁-C₆)-alkyl, whereinthe alkyl is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R13, 5) —(C₀-C₆)-alkyl-(C₆-C₁₄)-aryl, wherein thealkyl and aryl are independently from one another unsubstituted ormono-, di- or trisubstituted by R13, 7) —O—R¹⁷, or 8)—(C₀-C₆)-alkyl-(C₄-C₁₅)-heterocyclyl, wherein the alkyl and heterocyclylare unsubstituted or mono-, di- or trisubstituted by R13, or R11 and R12together with the nitrogen atom to which they are bonded form azepine,azetidine, 1,4-diazepane, dioxazole, dioxazine, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, imidazole, imidazoline, imidazolidine,isothiazole, isothiazolidine, isothiazoline, isoxazole, isoxazoline,isoxazolidine, 2-isoxazoline, ketopiperazine, morpholine,[1,4]oxazepane, oxazole, piperazine, piperidine, pyrazine, pyrazole,pyrazoline, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole,pyrrolidine, pyrrolidinone, pyrroline, tetrahydropyridine, tetrazine,tetrazole, thiazole, thiadiazole, thiazolidine, thiazoline,thiomorpholine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole or 1,2,4-triazole, each of which is unsubstituted ormono-, di- or trisubstituted independently of one another by R13; R13 isfluorine, chlorine, bromine, iodine, —NO₂, —CN, ═O, —OH, —CF₃,—C(O)—O—R¹⁰, —C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰, —(C₀-C₃)-alkylene-O—R¹⁰,—Si—(CH₃)₃, —N(R¹⁰)—S(O)₂—R¹⁰, —S—R¹⁰, —SO₂—R¹⁰, —S(O)₂—N(R¹⁰)—R²⁰,—C(O)—R¹⁰, —(C₁-C₈)-alkyl, —(C₁-C₈)-alkoxy, phenyl, phenyloxy-, —O—CF₃,—(C₁-C₃)-perfluoroalkyl, —(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—R17,—(C₁-C₄)-alkoxy-phenyl, —(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—O—R17,—O—R15, —NH—C(O)—NH—R¹⁰, —NH—C(O)—O—R¹⁰, or a residue selected from thegroup consisting of

wherein Me is methyl; and R15 and R16 are independently of one anotherhydrogen, —(C₁-C₆)-alkyl, or together form cyclopropyl, cyclobutyl,cyclopentyl or cyclohexyl, wherein each ring is unsubstituted orsubstituted one to three times by R¹⁰.
 5. The compound according toclaim 1, wherein R0 as 1) is phenyl, wherein the phenyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R8, or3) a heterocycyclyl selected from the group consisting of pyridyl,2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl,furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl,pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl,triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein theheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R8, and in addition is substituted bypyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl,3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl,imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl,isothiazolyl, triazolyl, tetrazolyl, pyridazinyl or pyrazinyl, each ofwhich is unsubstituted or mono-, di- or trisubstituted independently ofone another by R8; R8 is 1) F, Cl, Br or I, 4) —C(O)—NH₂, 9)—(C₁-C₄)-alkyl, wherein the alkyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by halogen, —OH or methoxy,or 10) —O—(C₁-C₄)-alkyl, wherein the alkyl is unsubstituted or mono-,di- or trisubstituted independently of one another by halogen ormethoxy, provided that R8 is at least one halogen, —C(O)—NH₂ or—O—(C₁-C₈)-alkyl; substructure D is a residue selected from the groupconsisting of phenyl, pyridyl, pyridyl-N-oxide, pyrrolyl, furyl,thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl,triazolyl, isothiazolyl, thiadiazolyl, pyrimidinyl, pyridazinyl andpyrazinyl, and is unsubstituted or substituted 1, 2, 3 or 4 times by R3;Q is a direct bond, —C(O)—, —SO₂— or —(C₁-C₆)-alkylene,—(C₀-C₂)-alkylene-C(O)—NR¹⁰— or—(C₀-C₃)-alkylene-C(O)—O—(C₀-C₂)-alkylene; R¹ is hydrogen,—(C₁-C₂)-alkyl, —(C₁-C₃)-alkylene-C(O)—NH—R⁰,—(C₁-C₃)-perfluoroalkylene, —(C₁-C₃)-alkylene-C(O)—O—R¹⁵,—(C₁-C₃)-alkylene-S(O)₂—(C₁-C₃)-alkyl or—(C₁-C₃)-alkylene-S(O)₂—N(R^(4′))—R^(5′), R² is a direct bond or—(C₁-C₂)-alkylene, or R¹-N—R²—V form azetidine, azetidinone, piperidine,piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole,1,2,4-triazole, tetrazine, tetrazole, 1,4-diazepane, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, azepine, ketopiperazine, 1,4-oxazepane,oxazole, isoxazole, isoxazolidine, 2-isoxazoline, morpholine, thiazole,isothiazole, thiadiazole or thiomorpholine, each of which isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R14; R14 is fluorine, chlorine, —OH, ═O, —(C₁-C₈)-alkyl,—C(O)—OH, —CN, —NH₂, —C(O)—O—(C₁-C₄)-alkyl, —C(O)—NH—(C₁-C₈)-alkyl,—C(O)—N—[(C₁-C₈)-alkyl]₂, —C(O)—NH₂ or —N(R¹⁸)—R²¹, wherein R¹⁸ and R²¹are independently from each other hydrogen, —(C₁-C₃)-perfluoroalkyl or—(C₁-C₄)-alkyl; V is 2) phenyl, wherein the phenyl is unsubstituted ormono-, di- or trisubstituted independently of one another by R14, or 3)a cyclic residue selected from the group consisting of azaindole(1H-pyrrolopyridine), aziridine, azirine, azetidine, azetidinone,1,4-diazepane, pyrrole, pyrrolidine, pyridonyl, imidazole, pyrazole,1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine, pyrimidine,pyrazine, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, tetrazine,tetrazole, azepine, diazirine, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, pyridazine, piperidine, piperazine, pyrrolidinone,ketopiperazine, furan, pyran, dioxole, 1,4-oxazepane, oxazole,isoxazole, 2-isoxazoline, isoxazolidine, morpholine, oxirane,oxaziridine, 1,3-dioxolene, 1,3-dioxolane, 1,2-oxazine, 1,3-oxazine,1,4-oxazine, oxaziridine, thiophene, thiopyran, thietan, thiazole,isothiazole, isothiazoline, isothiazolidine, 1,2-oxathiolan,thiodiazole, thiopyran, 1,2-thiazine, 1,3-thiazole, 1,3-thiazine,1,4-thiazine, thiadiazine and thiomorpholine, wherein sthe cyclicresidue is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R14; G is a direct bond, —(CH₂)_(m)—, or—(CH₂)_(m)—NR¹⁰—; m is zero, 1, 2, 3 or 4; M is 1) hydrogen, 2)—(C₁-C₆)-alkyl, wherein the alkyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R14, 3) —C(O)—N(R¹¹)—R¹²,or 6) heterocyclyl, wherein the heterocyclyl is selected from the groupconsisting of azepane, azepine, 1,4-diazepane, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, imidazole, isothiazole, isoxazole,isoxazolidine, 2-isoxazoline, ketomorpholine, ketopiperazine,morpholine, oxazole, [1,4]-oxazepane, piperazine, piperazinone,piperidine, piperidinone, pyrazine, pyridazine, pyridazinone, pyridine,pyridone, pyrimidine, pyrrolidine, pyrrolidinone, tetrahydropyran,1,4,5,6-tetrahydro-pyridazinyl, tetrazine, tetrazole, thiadiazole,thiazole, thiomorpholine, thiophene, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,3-triazole and 1,2,4-triazole, wherein theheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R14, or 7) (C₃-C₆)-cycloalkyl; R3 is 1)hydrogen, 2) halogen, 3) —(C₁-C₄)-alkyl, wherein the alkyl isunsubstituted or mono-, di- or trisubstituted independently of oneanother by R13, 4) —(C₁-C₃)-perfluoroalkyl, 5) phenyl, wherein thephenyl is unsubstituted or mono-, di- or trisubstituted independently ofone another by R13, 6) —(C₀-C₄)-alkylene-O—R19, 8) —CN, 8)—NR¹⁰—SO₂—R¹⁰, 9) —SO_(s)—R¹¹, wherein s is 1 or 2, 10)—SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2, 11) —(C₀-C₄)-alkylene-C(O)—R¹¹,12) —(C₀-C₄)-alkylene-C(O)—O—R ¹¹, 13)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹², 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹², 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl, 18)—C(O)—O—C(R15, R16)—O—C(O)—R17, 19)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl, 20)—C(O)—O—C(R15, R16)—O—C(O)—O—R17, 25)—(C₀-C₃)-alkylene-O—CH₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,—(C₀-C₃)-alkylene-O—CH₂—CF₂—CF₂—CH₂—O—(C₀-C₃)-alkyl, or—(C₀-C₃)-alkylene-O—CH₂-(C₁-C₃)-perfluoroalkylene-CH₂—OH, 26)—SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2, 27)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³, 28) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or29) a residue selected from the group consisting of

 wherein Me is methyl; two —OR19 residues and adjacent atoms throughwhich they are attached may form a 1,3-dioxole ring or a2,3-dihydro-[1,4]dioxine ring, each of which is substituted one, two,three or four times by R13; R¹¹ and R¹² together with the nitrogen atomto which they are bonded may form azepine, azetidine, 1,4-diazepane,dioxazole, dioxazine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine,imidazole, imidazoline, imidazolidine, isothiazole, isothiazolidine,isothiazoline, isoxazole, isoxazoline, isoxazolidine, 2-isoxazoline,ketopiperazine, morpholine, [1,4]-oxazepane, oxazole, piperazine,piperidine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine,pyridine, pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, pyrroline,tetrahydropyridine, tetrazine, tetrazole, thiazole, thiadiazole,thiazolidine, thiazoline, thiomorpholine, thiophene, 1,2,3-triazine,1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole or 1,2,4-triazole, eachof which is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R13; R13 is fluorine, chlorine, —NO₂, —CN, ═O, —OH,—CF₃, —C(O)—O—R¹⁰, —C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰,—(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —N(R¹⁰)—S(O)₂—R¹⁰, —S—R¹⁰,—SO₂—R¹⁰, —S(O)₂—N(R¹⁰)—R²⁰, —C(O)—R¹⁰, —(C₁-C₈)-alkyl, —(C₁-C₈)-alkoxy,phenyl, phenyloxy-, —O—CF₃, —(C₁-C₃)-perfluoroalkyl, —NH—C(O)—NH—R¹⁰,—(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—R17, —(C₁-C₄)-alkoxy-phenyl,—(C₀-C₄)-alkyl-C(O)—O—C(R15, R16)—O—C(O)—O—R17, —O—R15, —NH—C(O)—O—R¹⁰,or a residue from the group consisting of

wherein Me is methyl; and R15 and R16 are independently of one anotherhydrogen, —(C₁-C₆)-alkyl, or together form cyclopropyl, cyclobutyl,cyclopentyl or cyclohexyl, wherein each ring is unsubstituted orsubstituted one to three times by R¹⁰
 6. The compound according to claim1, wherein R0 as 1) phenyl, wherein the phenyl is unsubstituted ormono-, di- or trisubstituted independently of one another by R8, or 3) aheterocyclyl selected from of the group consisting of pyridyl,2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl, 3-pyrrolyl,furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl, imidazolyl,pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl,triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, wherein theheterocyclyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R8, and in addition is substituted bypyridyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, 2-pyrrolyl,3-pyrrolyl, furyl, 2-furyl, 3-furyl; thienyl, 2-thienyl, 3-thienyl,imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl,isothiazolyl, triazolyl, tetrazolyl, pyridazinyl and pyrazinyl, each ofwhich is unsubstituted or mono-, di- or trisubstituted independently ofone another by R8; R8 is 1) F, Cl, Br, or I, 4) —C(O)—NH₂, 9)—(C₁-C₄)-alkyl, wherein the alkyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by halogen, —OH or methoxy,or 10) —O—(C₁-C₄)-alkyl, wherein the alkyl is unsubstituted or mono-,di- or trisubstituted independently of one another by halogen ormethoxy, provided that R8 is at least one halogen, —C(O)—NH₂ or—O—(C₁-C₈)-alkyl; substructure D is a residue selected from the groupconsisting of phenyl, pyridyl, pyridyl-N-oxide, pyrrolyl, furyl,thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl,triazolyl, isothiazolyl, thiadiazolyl, pyrimidinyl, pyridazinyl andpyrazinyl, and is unsubstituted or substituted 1, 2, 3 or 4 times by R³;Q is a direct bond, —C(O)—, —SO₂— —C(O)—O-methylene, —(C₁-C₆)-alkylen or—(C₀-C₂)-alkylen-C(O)—NR¹⁰—; R¹ is hydrogen or —(C₁-C₂)-alkyl, R² is adirect bond or —(C₁-C₂)-alkylen, or R¹—N—R²—V form piperidine,piperazine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole,1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole,isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole,thiadiazole or thiomorpholine, each of which is unsubstituted or mono-,di- or trisubstituted independently of one another by R14; R14 isfluoro, chlorine, —(C₁-C₄)-alkyl or —NH₂; V is 2) phenyl, wherein thephenyl is unsubstituted or mono-, di- or trisubstituted independently ofone another by R14, or 3) a cyclic residue selected from the groupconsisting of azaindolyl (1H-pyrrolopyridyl), azetidine, azepine,aziridine, azirine, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, diazirine, 1,3-dioxolane, dioxazole, furan, imidazole,isoquinoline, isothiazole, isothiazolidine, isothiazoline, isoxazole,2-isoxazoline, isoxazolidine, ketopiperazine, morpholine, 1,2-oxazine,1,3-oxazine, 1,4-oxazine, oxazole, 1,2-oxathiolan, piperidine, pyran,pyrazine, pyrazole, pyridazine, piperazine, pyridine, pyridone,pyrimidine, pyrrole, pyrrolidine, pyrrolidinone, quinazoline, quinoline,tetrazine, tetrazole, thiadiazine, 1,2-thiazine, 1,3-thiazine,1,4-thiazine, 1,3-thiazole, thietan, thiomorpholine, thiophene,thiopyran, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine,1,2,3-triazole and 1,2,4-triazole, each of which is unsubstituted ormono-, di- or trisubstituted independently of one another by R14; G is adirect bond, —(CH₂)_(m)—, or —(CH₂)_(m)—NR¹⁰—; m is zero, 1, 2, 3 or 4;M is 1) hydrogen, 2) —(C₁-C₆)-alkyl, wherein alkyl is unsubstituted ormono-, di- or trisubstituted independently of one another by R14, 3)—C(O)—N(R¹¹)—R¹², or 6) heterocyclyl, wherein the heterocyclyl isselected from the group consisting of 1,4-diazepane, ketomorpholine,thiophene, pyridazone, piperidine, piperazine, pyridine, pyrimidine,pyrrolidine, pyrrolidinone, pyridonyl, imidazole, pyridazine, pyrazine,1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-triazole,1,2,4-triazole, tetrazine, tetrazole, 1,2-diazepine, 1,3-diazepine,1,4-diazepine, azepine, ketopiperazine, oxazole, isoxazole,isoxazolidine, 2-isoxazoline, morpholine, thiazole, isothiazole,tetrahydropyran, 1,4,5,6-tetrahydro-pyridazinyl, thiadiazole orthiomorpholine, wherein the heterocyclyl is unsubstituted or mono-, di-or trisubstituted independently of one another by R14, or 7)(C₃-C₆)-cycloalkyl; R3 is 1) hydrogen, 2) halogen, 3) —(C₁-C₄)-alkyl,wherein the alkyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R13, 4) —(C₁-C₃)-perfluoroalkyl, 5)phenyl, wherein the phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13, 6)—(C₀-C₄)-alkylene-O—R19, 8) —CN, 8) —NR¹⁰—SO₂—R¹⁰, 9) —SO_(s)—R¹¹,wherein s is 1 or 2, 10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2, 11)—(C₀-C₄)-alkylene-C(O)—R¹¹, 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹, 13)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹², 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹², 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl, 18)—C(O)—O—C(R15, R16)—O—C(O)—R17, 19)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl, 20)—C(O)—O—C(R15, R16)—O—C(O)—O—R17, 26)—(C₀-C₃)-alkylene-O—CH₂—CF₂—CH₂—O—(C₀-C₃)-alkyl,—(C₀-C₃)-alkylene-O—CH₂—CF₂—CF₂—CH₂—O—(C₀-C₃)-alkyl, or—(C₀-C₃)-alkylene-O—CH₂-(C₁-C₃)-perfluoroalkylene-CH₂—OH, 26)—SO_(w)—N(R¹¹)—R¹³, wherein w is 1 or 2, 27)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³, 28) —(C₀-C₄)-alkylene-N(R¹¹)—R¹³, or29) a residue selected from the group consisting of

 wherein Me is methyl; R19 is a) hydrogen, b) —(C₁-C₄)-alkyl, whereinthe alkyl is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R13, or c) phenyl, wherein the phenyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R13, d)—CF₃, or e) —CHF₂; R11 and R12 are independently of one anotheridentical or different and are 1) hydrogen, 2) —(C₁-C₄)-alkyl, whereinthe alkyl is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R13, 3) —(C₀-C₆)-alkyl-(C₃-C₆)-cycloalkyl, 7) —O—R¹⁷,or 8) —(C₀-C₆)-alkyl-(C₄-C₁₅)-heterocyclyl, wherein the alkyl andheterocyclyl independently from one another are unsubstituted or mono-,di- or trisubstituted by R13 and wherein the heterocyclyl azetidine,cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine, morpholine,(1,4)-oxazepane, oxazolidine, piperidine, piperazine, pyrrolidine,tetrahydrothiophene, thiazolidine or thiomorpholine, or R11 and R12together with the nitrogen atom to which they are bonded form azetidine,cyclopropyl, cyclobutyl, 4,5-dihydro-oxazole, imidazolidine, morpholine,(1,4)-oxazepane, oxazolidine, piperidine, piperazine, pyrrolidine,tetrahydrothiophene, thiazolidine or thiomorpholine; R13 is fluorine,—CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰, —C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰,—(C₃-C₆)-cycloalkyl, —(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —S—R¹⁰,—SO₂—R¹⁰, —(C₁-C₃)-perfluoroalkyl, or a residue selected from the groupconsisting of

 wherein Me is methyl; R¹⁰ and R²⁰ are independently of one anotherhydrogen, —(C₁-C₄)-alkyl or —(C₁-C₃)-perfluoroalkyl; and R¹⁵ and R¹⁶ areindependently of one another hydrogen, —(C₁-C₄)-alkyl, or together formcyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring isunsubstituted or substituted one to three times by R¹⁰.
 7. The compoundaccording to claim 1, wherein R0 is 1) phenyl, wherein the phenyl isunsubstituted or mono- or disubstituted independently of one another byR8, 2) pyridyl, wherein the pyridyl is unsubstituted or mono- ordisubstituted independently of one another by R8, or 3) a heterocyclylselected from the group consisting of thienyl, thiadiazolyl, isoxazolyland thiazolyl, wherein the heterocyclyl is substituted by thienyl,2-thienyl and 3-thienyl, each of which is unsubstituted or mono- ordisubstituted independently of one another by R8; R8 is F, Cl, Br,—OCH₃, —C(O)—NH₂ or —O—CF₃; substructure D is a residue selected fromthe group consisting of phenyl, pyridyl, pyridyl-N-oxide, pyrrolyl,thienyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl,isothiazolyl, thiadiazolyl, pyrimidinyl, pyridazinyl and pyrazinyl, andis unsubstituted or substituted 1, 2, 3 or 4 times by R3; Q is a directbond, —C(O)—, —SO₂—, —C(O)—O-methylene, —CH₂—C(O)—NH—, methylene orethylene; R¹ is hydrogen, R² is a direct bond or methylene, or R¹—N—R²—Vform azetidine, pyrrolidine, piperidine or piperazine; R14 is fluorine,chlorine, methyl, ethyl, ═O, —SO₂—CH₃ or —NH₂; V is 2) phenyl, whereinphenyl is unsubstituted or mono- or disubstituted independently of oneanother by R14, or 3) azaindolyl (1H-pyrrolopyridyl), azetidine,1,4-diazepane, isoxazole, isoquinoline, piperazine, piperidine,pyrazine, pyridazine, pyrimidine, pyrrolidine, quinazoline, quinoline ortetrahydropyrane, each of which is unsubstituted or mono- ordisubstituted independently of one another by R14; G is a direct bond,—(CH₂)_(m)—, —C(O)— or —(CH₂)_(m)—NR¹⁰—; m is zero, 1 or 2; M is 1)hydrogen, 2) (C₂-C₄)-alkyl, wherein the alkyl is unsubstituted or mono-or disubstituted independently of one another by R14, or 6) azepanyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolyl,ketomorpholinyl, morpholinyl, [1,4]Oxazepanyl, piperidinyl, phenyl,piperidonyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidyl,pyrrolidinyl, 1,4,5,6-tetrahydro-pyridazinyl, or tetrahydropyranyl, eachof which is unsubstituted or mono- or disubstituted independently of oneanother by R14; R3 is 1) hydrogen, 2) F or Cl, 3) —(C₁-C₄)-alkyl,wherein the alkyl is unsubstituted or mono-, di- or trisubstitutedindependently of one another by R13, 4) —(C₁-C₃)-perfluoroalkyl, 5)phenyl, wherein the phenyl is unsubstituted or mono-, di- ortrisubstituted independently of one another by R13, 6)—(C₀-C₂)-alkylene-O—R19, 8) —CN, 9) —SO_(s)—R¹¹, wherein s is 1 or 2,10) —SO_(t)—N(R¹¹)—R¹², wherein t is 1 or 2, 11)—(C₀-C₄)-alkylene-C(O)—R¹¹, 12) —(C₀-C₄)-alkylene-C(O)—O—R¹¹, 13)—(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹², 14) —(C₀-C₄)-alkylene-N(R¹¹)—R¹², 15)—NR¹⁰—SO₂—R¹⁰, 17)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—(C₁-C₄)-alkyl, 18)—C(O)—O—C(R15, R16)—O—C(O)—R17, 19)—(C₀-C₂)alkylene-C(O)—O—(C₂-C₄)-alkylene-O—C(O)—O—(C₁-C₆)-alkyl, 20)—C(O)—O—C(R15, R16)—O—C(O)—O—R17, 27) —(C₀-C₄)-alkylene-C(O)—N(R¹¹)—R¹³or 29) a residue selected from the group consisting of

 wherein Me is methyl; R19 is a) hydrogen, b) —(C₁-C₄)-alkyl, whereinthe alkyl is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R13, or c) phenyl, wherein the phenyl is unsubstitutedor mono-, di- or trisubstituted independently of one another by R13, d)—CF₃, or e) —CHF₂; R11 and R12 are independently of one anotheridentical or different and are 1) hydrogen, 2) —(C₁-C₄)-alkyl, whereinthe alkyl is unsubstituted or mono-, di- or trisubstituted independentlyof one another by R13, 3) —(C₀-C₆)-alkyl-(C₃-C₆)-cycloalkyl, 7) —O—R¹⁷,or 8) —(C₀-C₆)-alkyl-(C₆-C₁₅)-heterocyclyl, wherein the alkyl andheterocyclyl independently from one another are unsubstituted or mono-,di- or trisubstituted by R13 and wherein the heterocyclyl is azetidine,imidazolidine, morpholine, 4,5-dihydro-[1,2,4]oxadiazole, -[1,3]dioxole,(1,4)-oxazepane or pyrrolidine, or R11 and R12 together with thenitrogen atom to which they are bonded form azetidine, imidazolidine,morpholine, (1,4)-oxazepane piperazine, piperidine, pyrrolidine orthiomorpholine; R13 is fluorine, —CN, ═O, —OH, —CF₃, —C(O)—O—R¹⁰,—C(O)—N(R¹⁰)—R²⁰, —N(R¹⁰)—R²⁰, —(C₃-C₆)-cycloalkyl,—(C₀-C₃)-alkylene-O—R¹⁰, —Si—(CH₃)₃, —S—R¹⁰, —SO₂—R¹⁰, —SO₂—NH,—(C₁-C₃)-perfluoroalkyl, —(C₁-C₃)-alkyl, or a residue selected from thegroup consisting of

 wherein Me is methyl; R¹⁰ and R²⁰ are independently of one anotherhydrogen, —(C₁-C₄)-alkyl or —(C₁-C₃)-perfluoroalkyl; and R¹⁵ and R¹⁶ areindependently of one another hydrogen, —(C₁-C₄)-alkyl, or together formcyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, wherein each ring isunsubstituted or substituted one to three times by R¹⁰.
 8. The compoundaccording to claim 1, wherein J₁ is N and J₂ is N—Q—R⁰.
 9. The compoundaccording to claim 1, wherein J₂ is N and J₁ is N—Q—R⁰.
 10. The compoundaccording to claim 1, wherein the compound is1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-6-carboxylicacid methyl ester,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-7-carboxylicacid methyl ester,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-7-carboxylicacid,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-6-carboxylicacid, Indazole-1,3-dicarboxylic acid1-[(5-chloro-pyridin-2-yl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 1-ethoxycarbonyloxy-ethyl ester,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,5-(Azetidine-1-carbonyl)-1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-methanesulfonyl-ethyl)-amide],1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-sulfamoyl-ethyl)-amide],1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2-morpholin-4-yl-ethyl)-amide],1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylic acid3-[(1-isopropyl-piperidin-4-yl)-amide]5-trimethylsilanylmethyl-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[bis-(2-hydroxy-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2-hydroxy-ethyl)-methyl-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-amino}-aceticacid ethyl ester,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2,2-difluoro-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-carbamoylmethyl-amide 3-[(1-isopropyl-piperidin-4-yl)-amide],1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 5-[(2-hydroxy-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-{[2-(2-oxo-imidazolidin-1-yl)-ethyl]-amide},1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid5-[(2-hydroxy-1-hydroxymethyl-1-methyl-ethyl)-amide]3-[(1-isopropyl-piperidin-4-yl)-amide],{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-amino}-aceticacid,1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylniethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-(2S)-azetidine-2-carboxylicacid,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid3-[(1-isopropyl-piperidin-4-yl)-amide]5-[(2,2,2-trifluoro-ethyl)-amide],{[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-methyl-amino}-aceticacid,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmnethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-hydroxy-ethyl ester,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-([1,4]oxazepane-4-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(3-hydroxy-azetidine-1-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3,5-dicarboxylicacid 3-[(1-isopropyl-piperidin-4-yl)-amide]5-(methoxy-amide),1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(piperidine-1-carbonyl)-phenyl]-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(pyrrolidine-1-carbonyl)-phenyl]-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(morpholine-4-carbonyl)-phenyl]-amide,1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(morpholine-4-carbonyl)-phenyl]-amide,1-(1-{1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carbonyl}-piperidin-4-yl)-pyrrolidin-2-one,N-(5-Chloro-pyridin-2-yl)-2-{3-[4-(2-oxo-pyrrolidin-1-yl)-piperidine-1-carbonyl]-indazol-1-yl}-acetamide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide,1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(2-oxo-pyrrolidin-1-yl)-phenyl]-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (2′-methanesulfonyl-biphenyl-4-yl)-amide,1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid (2′-methanesulfonyl-biphenyl-4-yl)-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid[4-(4-methyl-6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenyl]-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (4-morpholin-4-yl-phenyl)-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(1H-imidazol-4-yl)-phenyl]-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid (4-piperidin-1-yl-phenyl)-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-[4-(3-oxo-morpholin-4-yl)-phenylcarbamoyl]-1H-indazole-5-carboxylicacid methyl ester,1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid methyl ester,1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-(cyanamide-1-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide,1-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carbonyl]-azetidine-3-carboxylicacid,1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(3-oxo-morpholin-4-yl)-phenyl]-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indazole-3-carboxylicacid [4-(4-oxo4H-pyridin-1-yl)-phenyl]-amide,1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-1H-indazole-3-carboxylicacid [4-(4-oxo-4H-pyridin-1-yl)-phenyl]-amide,1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-methoxy-ethyl ester,1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-3-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-indazole-5-carboxylicacid 2-hydroxy-ethyl ester, or1-[(5-Chloro-pyridin-2-ylcarbamoyl)-methyl]-5-([1,4]oxazepane-4-carbonyl)-1H-indazole-3-carboxylicacid (1-isopropyl-piperidin-4-yl)-amide.
 11. A process for thepreparation of a compound according to claim 1, wherein J₁ is N and J₂is N—Q—R⁰, which comprises condensing a compound of the formula 7 with acompound of the formula HR^(8′) to give a compound of the formula 8 andconverting the compound of the formula 8 into a compound of the formulaI, wherein J₁ is N and J₂ is N—Q—R⁰,

wherein the residue R^(8′) has the donation of —N(R¹)—R²—V-G-M asindicated in claim 1, but where in R^(8′) functional groups can also bepresent in the form of groups that are subsequently transformed into thefinal functional groups present in —N(R¹)—R²—V-G-M, and where theresidue R¹³⁶ denotes the group -Q-R⁰ or can denote a group which issubsequently transformed into the group -Q-R⁰, and where the group—C(O)—R¹³⁵ can be a carboxylic acid group or derivatives thereof, andwhere the groups R³ in the formulae 7 and 8 have the correspondingdefinitions of R³ in formula I as defined in claim 1 functional groupsin them can also be present in protected form or in the form ofprecursor groups.
 12. A process for the preparation of a compoundaccording to claim 1, wherein J₂ is N and J₁ is N—Q—R⁰, which comprisescondensing a compound of the formula 9 with a compound of the formulaHR^(8′) to give a compound of the formula 10 and optionally convertingthe compound of the formula 10 into a compound according of formula I,wherein J₂ is N and J₁ is N—Q—R⁰,

wherein the residue R^(8′) has the donation of —N(R¹)—R²—V-G-M asindicated in claim 1, but where in R^(8′) functional groups can also bepresent in the form of groups that are subsequently transformed into thefinal functional groups present in —N(R¹)—R²—V-G-M, and where theresidue R¹³⁶ denotes the group -Q-R⁰ or can denote a group which issubsequently transformed into the group -Q-R⁰, and where the group—C(O)—R¹³⁵ can be a carboxylic acid group or derivatives thereof, andwhere the groups R³ in the formulae 9 and 10 have the correspondingdefinitions of R³ in formula Ib as defined in claim 1 or functionalgroups in them can also be present in protected form or in the form ofprecursor groups.
 13. A pharmaceutical composition comprising at leastone compound according to claim 1 and a pharmaceutically acceptablecarrier.
 14. A method for inhibiting factor Xa in a patient in needthereof, comprising administering to the patient a pharmaceuticallyeffective amount of a compound according to claim
 1. 15. A method forinhibiting factor VIIa in a patient in need thereof, comprisingadministering to the patient a pharmaceutically effective amount of acompound according to claim
 1. 16. A method for influencing bloodcoagulation in a patient in need thereof, comprising administering tothe patient a pharmaceutically effective amount of a compound accordingto claim
 1. 17. A method for inhibiting influencing blood fibrinolysisin a patient in need thereof, comprising administering to the patient apharmaceutically effective amount of a compound according to claim 1.18. A method for treating abnormal thrombus formation, acute myocardialinfarction, cardiovascular disorders, unstable angina, thromboembolism,acute vessel closure associated with thrombolytic therapy orpercutaneous transluminal coronary angioplasty (PTCA), transientischemic attacks, stroke, intermittent claudication, bypass grafting ofthe coronary or peripheral arteries, vessel luminal narrowing,restenosis post coronary or venous angioplasty, maintenance of vascularaccess patency in long-term hemodialysis patients, pathologic thrombusformation occurring in the veins of the lower extremities followingabdominal, knee or hip surgery, pathologic thrombus formation occurringin the veins of the lower extremities following abdominal, knee and hipsurgery, a risk of pulmonary thromboembolism, or disseminated systemicintravascular coagulatopathy occurring in vascular systems during septicshock, viral infections or cancer, or reducing an inflammatory response,fibrinolysis, or treatment of coronary heart disease, myocardialinfarction, angina pectoris, vascular restenosis, for example restenosisfollowing angioplasty like PTCA, adult respiratory distress syndrome,multi-organ failure and disseminated intravascular clotting disorder,deep vein or proximal vein thrombosis, which can occur followingsurgery, in a patient in need thereof, comprising administering to thepatient a pharmaceutically effective amount of a compound according toclaim 1.